Posts tagged white matter
Articles and news from the latest research reports.
Bioengineers Create Functional 3D Brain-like Tissue
Bioengineers have created three-dimensional brain-like tissue that functions like and has structural features similar to tissue in the rat brain and that can be kept alive in the lab for more than two months.
As a first demonstration of its potential, researchers used the brain-like tissue to study chemical and electrical changes that occur immediately following traumatic brain injury and, in a separate experiment, changes that occur in response to a drug. The tissue could provide a superior model for studying normal brain function as well as injury and disease, and could assist in the development of new treatments for brain dysfunction.
The brain-like tissue was developed at the Tissue Engineering Resource Center at Tufts University, Boston, which is funded by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) to establish innovative biomaterials and tissue engineering models. David Kaplan, Ph.D., Stern Family Professor of Engineering at Tufts University is director of the center and led the research efforts to develop the tissue.
Currently, scientists grow neurons in petri dishes to study their behavior in a controllable environment. Yet neurons grown in two dimensions are unable to replicate the complex structural organization of brain tissue, which consists of segregated regions of grey and white matter. In the brain, grey matter is comprised primarily of neuron cell bodies, while white matter is made up of bundles of axons, which are the projections neurons send out to connect with one another. Because brain injuries and diseases often affect these areas differently, models are needed that exhibit grey and white matter compartmentalization.
Recently, tissue engineers have attempted to grow neurons in 3D gel environments, where they can freely establish connections in all directions. Yet these gel-based tissue models don’t live long and fail to yield robust, tissue-level function. This is because the extracellular environment is a complex matrix in which local signals establish different neighborhoods that encourage distinct cell growth and/or development and function. Simply providing the space for neurons to grow in three dimensions is not sufficient.
Now, in the Aug. 11th early online edition of the journal Proceedings of the National Academy of Sciences, a group of bioengineers report that they have successfully created functional 3D brain-like tissue that exhibits grey-white matter compartmentalization and can survive in the lab for more than two months.
“This work is an exceptional feat,” said Rosemarie Hunziker, Ph.D., program director of Tissue Engineering at NIBIB. “It combines a deep understand of brain physiology with a large and growing suite of bioengineering tools to create an environment that is both necessary and sufficient to mimic brain function.”
The key to generating the brain-like tissue was the creation of a novel composite structure that consisted of two biomaterials with different physical properties: a spongy scaffold made out of silk protein and a softer, collagen-based gel. The scaffold served as a structure onto which neurons could anchor themselves, and the gel encouraged axons to grow through it.
To achieve grey-white matter compartmentalization, the researchers cut the spongy scaffold into a donut shape and populated it with rat neurons. They then filled the middle of the donut with the collagen-based gel, which subsequently permeated the scaffold. In just a few days, the neurons formed functional networks around the pores of the scaffold, and sent longer axon projections through the center gel to connect with neurons on the opposite side of the donut. The result was a distinct white matter region (containing mostly cellular projections, the axons) formed in the center of the donut that was separate from the surrounding grey matter (where the cell bodies were concentrated).
Over a period of several weeks, the researchers conducted experiments to determine the health and function of the neurons growing in their 3D brain-like tissue and to compare them with neurons grown in a collagen gel-only environment or in a 2D dish. The researchers found that the neurons in the 3D brain-like tissues had higher expression of genes involved in neuron growth and function. In addition, the neurons grown in the 3D brain-like tissue maintained stable metabolic activity for up to five weeks, while the health of neurons grown in the gel-only environment began to deteriorate within 24 hours. In regard to function, neurons in the 3D brain-like tissue exhibited electrical activity and responsiveness that mimic signals seen in the intact brain, including a typical electrophysiological response pattern to a neurotoxin.
Because the 3D brain-like tissue displays physical properties similar to rodent brain tissue, the researchers sought to determine whether they could use it to study traumatic brain injury. To simulate a traumatic brain injury, a weight was dropped onto the brain-like tissue from varying heights. The researchers then recorded changes in the neurons’ electrical and chemical activity, which proved similar to what is ordinarily observed in animal studies of traumatic brain injury.
Kaplan says the ability to study traumatic injury in a tissue model offers advantages over animal studies, in which measurements are delayed while the brain is being dissected and prepared for experiments. “With the system we have, you can essentially track the tissue response to traumatic brain injury in real time,” said Kaplan. “Most importantly, you can also start to track repair and what happens over longer periods of time.”
Kaplan emphasized the importance of the brain-like tissue’s longevity for studying other brain disorders. “The fact that we can maintain this tissue for months in the lab means we can start to look at neurological diseases in ways that you can’t otherwise because you need long timeframes to study some of the key brain diseases,” he said.
Hunziker added, “Good models enable solid hypotheses that can be thoroughly tested. The hope is that use of this model could lead to an acceleration of therapies for brain dysfunction as well as offer a better way to study normal brain physiology.”
Kaplan and his team are looking into how they can make their tissue model more brain-like. In this recent report, the researchers demonstrated that they can modify their donut scaffold so that it consists of six concentric rings, each able to be populated with different types of neurons. Such an arrangement would mimic the six layers of the human brain cortex, in which different types of neurons exist.
As part of the funding agreement for the Tissue Engineering Resource Center, NIBIB requires that new technologies generated at the center be shared with the greater biomedical research community.
“We look forward to building collaborations with other labs that want to build on this tissue model,” said Kaplan.
Kids with Autism, Sensory Processing Disorders Show Brain Wiring Differences
Researchers at UC San Francisco have found that children with sensory processing disorders have decreased structural brain connections in specific sensory regions different than those in autism, further establishing SPD as a clinically important neurodevelopmental disorder.
The research, published in the journal PLOS ONE, is the first study to compare structural connectivity in the brains of children with an autism diagnosis versus those with an SPD diagnosis, and with a group of typically developing boys. This new research follows UCSF’s groundbreaking study published in 2013 that was the first to find that boys affected with SPD have quantifiable regional differences in brain structure when compared to typically developing boys. This work showed a biological basis for the disease but prompted the question of how these differences compared with other neurodevelopmental disorders.
“With more than 1 percent of children in the U.S. diagnosed with an autism spectrum disorder, and reports of 5 to 16 percent of children having sensory processing difficulties, it’s essential we define the neural underpinnings of these conditions, and identify the areas they overlap and where they are very distinct,” said senior author Pratik Mukherjee, MD, PhD, a professor of radiology and biomedical imaging and bioengineering at UCSF.
SPD Gains Recognition as Distinct Condition
SPD can be hard to pinpoint, as more than 90 percent of children with autism also are reported to have atypical sensory behaviors, and SPD has not been listed in the Diagnostic and Statistical Manual used by psychiatrists and psychologists.
“One of the most striking new findings is that the children with SPD show even greater brain disconnection than the kids with a full autism diagnosis in some sensory-based tracts,” said Elysa Marco, MD, cognitive and behavioral child neurologist at UCSF Benioff Children’s Hospital San Francisco and the study’s corresponding author. “However, the children with autism, but not those with SPD, showed impairment in brain connections essential to the processing of facial emotion and memory.”
Children with SPD struggle with how to process stimulation, which can cause a wide range of symptoms including hypersensitivity to sound, sight and touch, poor fine motor skills and easy distractibility. Some SPD children cannot tolerate the sound of a vacuum, while others can’t hold a pencil or struggle with emotional regulation. Furthermore, a sound that is an irritant one day can be tolerated the next. The disease can be baffling for parents and has been a source of much controversy for clinicians who debate whether it constitutes its own disorder, according to the researchers.
“These kids, however, often don’t get supportive services at school or in the community because SPD is not yet a recognized condition,” said Marco. “We are starting to catch up with what parents already knew; sensory challenges are real and can be measured both in the lab and the real world. Our next challenge is to find the reason why children have SPD and move these findings from the lab to the clinic.”
Examining White Matter Tracts in the Brain
In the study, researchers used an advanced form of MRI called diffusion tensor imaging (DTI), which measures the microscopic movement of water molecules within the brain in order to give information about the brain’s white matter tracts. The brain’s white matter forms the “wiring” that links different areas of the brain and is therefore essential for perceiving, thinking and action. DTI shows the direction of the white matter fibers and the integrity of the white matter, thereby mapping the structural connections between brain regions.
The study examined the structural connectivity of specific white matter tracts in16 boys with SPD and 15 boys with autism between the ages of 8 and 12 and compared them with 23 typically developing boys of the same age range.
The researchers found that both the SPD and autism groups showed decreased connectivity in multiple parieto-occipital tracts, the areas that handle basic sensory information in the back area of the brain. However, only the autism cohort showed impairment in the inferior fronto-occipital fasciculi (IFOF), inferior longitudinal fasciculi (ILF), fusiform-amygdala and the fusiform-hippocampus tracts – critical tracts for social-emotional processing.
“One of the classic features of autism is decreased eye-to-eye gaze, and the decreased ability to read facial emotions,” said Marco. “The impairment in this specific brain connectivity, not only differentiates the autism group from the SPD group but reflects the difficulties patients with autism have in the real world. In our work, the more these regions are disconnected, the more challenge they are having with social skills.”
Kids with isolated SPD showed less connectivity in the basic perception and integration tracts of the brain that serve as connections for the auditory, visual and somatosensory (tactile) systems involved in sensory processing.
“If we can start by measuring a child’s brain connectivity and seeing how it is playing out in a child’s functional ability, we can then use that measure as a metric for success in our interventions and see if the connectivities are changing based on our clinical interventions,” said Marco. “Larger studies to replicate this early work are clearly needed but we are encouraged that DTI can be a powerful clinical and research tool for understanding the basis for sensory neurodevelopmental differences.”
Exposure to TV Violence Related to Irregular Attention and Brain Structure
Young adult men who watched more violence on television showed indications of less mature brain development and poorer executive functioning, according to the results of an Indiana University School of Medicine study published online in the journal Brain and Cognition.
The researchers used psychological testing and MRI scans to measure mental abilities and volume of brain regions in 65 healthy males with normal IQ between the age of 18 and 29, specifically chosen because they were not frequent video game players.
Lead author Tom A. Hummer, Ph.D., assistant research professor in the IU Department of Psychiatry, said the young men provided estimates of their television viewing over the past year and then kept a detailed diary of their TV viewing for a week. Participants also completed a series of psychological tests measuring inhibitory control, attention and memory. At the conclusion, MRI scans were used to measure brain structure.
Executive function is the broad ability to formulate plans, make decisions, reason and problem-solve, regulate attention, and inhibit behavior in order to achieve goals.
"We found that the more violent TV viewing a participant reported, the worse they performed on tasks of attention and cognitive control," Dr. Hummer said. "On the other hand, the overall amount of TV watched was not related to performance on any executive function tests."
Dr. Hummer noted that these executive functioning abilities can be important for controlling impulsive behaviors, including aggression. “The worry is that more impulsivity does not mix well with the behaviors modeled in violent programming.”
Tests that measured working memory, another subtype of executive functioning, were not found to be related to overall or violent TV viewing.
Comparing TV habits to brain images also produced results that Dr. Hummer and colleagues believe are significant.
"When we looked at the brain scans of young men with higher violent television exposure, there was less volume of white matter connecting the frontal and parietal lobes, which can be a sign of less maturity in brain development," he said.
White matter is tissue in the brain that insulates nerve fibers connecting different brain regions, making functioning more efficient. In typical development, the amount or volume of white matter increases as the brain makes more connections until about age 30, improving communication between regions of the brain. Connections between the frontal and parietal lobes are thought to be especially important for executive functioning.
"The take-home message from this study is the finding of a relationship between how much violent television we watch and important aspects of brain functioning like controlled attention and inhibition," Dr. Hummer said.
Dr. Hummer cautions that more research is needed to better understand the study findings.
"With this study we could not isolate whether people with poor executive function are drawn to programs with more violence or if the content of the TV viewing is responsible for affecting the brain’s development over a period of time," Dr. Hummer said. "Additional longitudinal work is necessary to resolve whether individuals with poor executive function and slower white matter growth are more drawn to violent programming or if exposure to media violence modifies development of cognitive control," Dr. Hummer said.
(Source: newswise.com)
In Old Age, Lack of Emotion and Interest May Signal Your Brain Is Shrinking
Older people who have apathy but not depression may have smaller brain volumes than those without apathy, according to a new study published in the April 16, 2014, online issue of Neurology®, the medical journal of the American Academy of Neurology. Apathy is a lack of interest or emotion.
“Just as signs of memory loss may signal brain changes related to brain disease, apathy may indicate underlying changes,” said Lenore J. Launer, PhD, with the National Institute on Aging at the National Institutes of Health (NIH) in Bethesda, MD, and a member of the American Academy of Neurology. “Apathy symptoms are common in older people without dementia. And the fact that participants in our study had apathy without depression should turn our attention to how apathy alone could indicate brain disease.”
Launer’s team used brain volume as a measure of accelerated brain aging. Brain volume losses occur during normal aging, but in this study, larger amounts of brain volume loss could indicate brain diseases.
For the study, 4,354 people without dementia and with an average age of 76 underwent an MRI scan. They were also asked questions that measure apathy symptoms, which include lack of interest, lack of emotion, dropping activities and interests, preferring to stay at home and having a lack of energy.
The study found that people with two or more apathy symptoms had 1.4 percent smaller gray matter volume and 1.6 percent less white matter volume compared to those who had less than two symptoms of apathy. Excluding people with depression symptoms did not change the results.
Gray matter is where learning takes place and memories are stored in the brain. White matter acts as the communication cables that connect different parts of the brain.
“If these findings are confirmed, identifying people with apathy earlier may be one way to target an at-risk group,” Launer said.
How brain structures grow as memory develops
Our ability to store memories improves during childhood, associated with structural changes in the hippocampus and its connections with prefrontal and parietal cortices. New research from UC Davis is exploring how these brain regions develop at this crucial time. Eventually, that could give insights into disorders that typically emerge in the transition into and during adolescence and affect memory, such as schizophrenia and depression.
Located deep in the middle of the brain, the hippocampus plays a key role in forming memories. It looks something like two curving fingers branching forward from a common root. Each branch is a folded-over structure, with distinct areas in the upper and lower fold.
“For a long time it was assumed that the hippocampus didn’t develop at all after the first couple of years of life,” said Joshua Lee, a graduate student at the UC Davis Department of Psychology and Center for Mind and Brain. Improvements in memory were thought to be due entirely to changes in the brain’s outer layers, or cortex, that manage attention and strategies. But that picture has begun to change in the past five years.
Recently, Lee, Professor Simona Ghetti at the Center for Mind and Brain and Arne Ekstrom, assistant professor in the UC Davis Center for Neuroscience, used magnetic resonance imaging to map the hippocampus in 39 children aged eight to 14 years.
While subfields of the hippocampus have been mapped in adult humans and animal studies, it’s the first time that they have been measured in children, Ghetti said.
“This is really important to us, because it allows us to understand the heterogeneity along the hippocampus, which has been examined in human adults and other species” Ghetti said.
Looking at three subregions — the cornu ammonis (CA) 1, CA3/dentate gyrus and subiculum — they found that the first two expanded with age, with the most pronounced growth in the right hippocampus. Only in the oldest 25 percent of the children, within a few months either side of 14, did the sizes of all three regions decrease.
When they tested the children for memory performance, children with a larger CA3/dentate gyrus tended to perform better, they found. The work was published online March 15 by the journal Neuroimage.
In a related study in collaboration with the laboratory of Professor Silvia Bunge at UC Berkeley, published March 27 in Cerebral Cortex, the researchers also demonstrated how white matter connections projecting from the hippocampus to the brain cortex are related to memory function in children.
“White matter” tracts connect the prefrontal and parietal regions of the brain cortex, which control how we pay attention to things and engage in memory strategies, with the media-temporal lobe, the area that includes the hippocampus.
In the study, children performed a memory test that prompted them either to actively memorize an item — and therefore engage the prefrontal and parietal cortices — or to view an image passively. The ability to successfully modulate attention was linked to development of white matter tracts linking the prefrontal and parietal cortex tothe mediatemporal lobe, Ghetti said, but not to fronto-parietal connections.
New research suggests connection between white matter and cognitive health
A multidisciplinary group of scientists from the Sanders-Brown Center on Aging at the University of Kentucky have identified an interesting connection between the health of the brain tissue that supports cognitive functioning and the presence of dementia in adults with Down syndrome.
Published in the Neurobiology of Aging, the study, which focused on detecting changes in the white matter connections of the brain, offers tantalizing potential for the identification of biomarkers connected to the development of dementia, including Alzheimer’s disease.
"We used magnetic resonance imaging to compare the health of the brain’s white matter and how strongly it connects different parts of the brain," explains Elizabeth Head, Ph.D., the study’s senior author. "The results indicate a compelling progression of deterioration in the integrity of white matter in the brains of our study participants commensurate with their cognitive health."
Research team member David Powell, PhD, compared the brain scans of three groups of volunteers: persons with Down syndrome but no dementia, persons with Down syndrome and dementia, and a healthy control group.
Using MRI technologies, brain scans of subjects with Down syndrome showed some compromise in the tissues of brain’s frontal lobe compared to those from the control group. When people with Down syndrome and dementia were compared to people with Down syndrome without dementia, those same white matter connections were even less healthy.
Perhaps the most intriguing aspect of the study was the correlation between the cognitive abilities of participants with Down Syndrome and the integrity of their white matter– those who had higher motor skill coordination and better learning and memory ability had healthier frontal white matter connections.
Persons with Down syndrome are at an extremely high risk for developing Alzheimer’s disease after the age of 40. The team hopes their work might eventually lead to the identification of biomarkers for the development of Alzheimer’s disease in people with Down syndrome and, potentially, extend that to the general population as well.
Head cautions that these results are to some extent exploratory due to the small cohort of 30 participants. But, she says, “If we are able to identify people who, based on biomarkers, have a higher risk of developing Alzheimer’s disease, we might be able to intervene at an earlier point to retard the progression of the disease.”
Blasts May Cause Brain Injury Even Without Symptoms
Veterans exposed to explosions who do not report symptoms of traumatic brain injury (TBI) may still have damage to the brain’s white matter comparable to veterans with TBI, according to researchers at Duke Medicine and the U.S. Department of Veterans Affairs.
The findings, published in the Journal of Head Trauma Rehabilitation on March 3, 2014, suggest that a lack of clear TBI symptoms following an explosion may not accurately reflect the extent of brain injury.
Veterans of recent military conflicts in Iraq and Afghanistan often have a history of exposure to explosive forces from bombs, grenades and other devices, although relatively little is known about whether this injures the brain. However, evidence is building – particularly among professional athletes – that subconcussive events have an effect on the brain.
"Similar to sports injuries, people near an explosion assume that if they don’t have clear symptoms – losing consciousness, blurred vision, headaches – they haven’t had injury to the brain,” said senior author Rajendra A. Morey, M.D., associate professor of psychiatry and behavioral sciences at Duke University School of Medicine and a psychiatrist at the Durham Veterans Affairs Medical Center. “Our findings are important because they’re showing that even if you don’t have symptoms, there may still be damage.”
Researchers in the Mid-Atlantic Mental Illness Research, Education and Clinical Center at the W.G. (Bill) Hefner Veterans Affairs Medical Center in Salisbury, N.C., evaluated 45 U.S. veterans who volunteered to participate in the study. The veterans, who served since September 2001, were split into three groups: veterans with a history of blast exposure with symptoms of TBI; veterans with a history of blast exposure without symptoms of TBI; and veterans without blast exposure. The study focused on veterans with primary blast exposure, or blast exposure without external injuries, and did not include those with brain injury from direct hits to the head.
To measure injury to the brain, the researchers used a type of MRI called Diffusion Tensor Imaging (DTI). DTI can detect injury to the brain’s white matter by measuring the flow of fluid in the brain. In healthy white matter, fluid moves in a directional manner, suggesting that the white matter fibers are intact. Injured fibers allow the fluid to diffuse.
White matter is the connective wiring that links different areas of the brain. Since most cognitive processes involve multiple parts of the brain working together, injury to white matter can impair the brain’s communication network and may result in cognitive problems.
Both groups of veterans who were near an explosion, regardless of whether they had TBI symptoms, showed a significant amount of injury compared to the veterans not exposed to a blast. The injury was not isolated to one area of the brain, and each individual had a different pattern of injury.
Using neuropsychological testing to assess cognitive performance, the researchers found a relationship between the amount of white matter injury and changes in reaction time and the ability to switch between mental tasks. However, brain injury was not linked to performance on other cognitive tests, including decision-making and organization.
“We expected the group that reported few symptoms at the time of primary blast exposure to be similar to the group without exposure. It was a surprise to find relatively similar DTI changes in both groups exposed to primary blast,” said Katherine H. Taber, Ph.D., a research health scientist at the W.G. (Bill) Hefner Veterans Affairs Medical Center and the study’s lead author. “We are not sure whether this indicates differences among individuals in symptoms-reporting or subconcussive effects of primary blast. It is clear there is more we need to know about the functional consequences of blast exposures.”
Given the study’s findings, the researchers said clinicians treating veterans should take into consideration a person’s exposure to explosive forces, even among those who did not initially show symptoms of TBI. In the future, they may use brain imaging to support clinical tests.
“Imaging could potentially augment the existing approaches that clinicians use to evaluate brain injury by looking below the surface for TBI pathology,” Morey said.
The researchers noted that the results are preliminary, and should be replicated in a larger study.
(Source: dukehealth.org)
Researchers Find Inherited Pathway of Risk for Schizophrenia
Schizophrenia is one of the most disabling of all psychiatric illnesses. Sadly, it is not uncommon and it strikes early in life.
Many studies have looked into causes and potential interventions, and it has been long known that genetic factors play a role in determining the risk of developing schizophrenia. However, recent work has shown that there will be no simple answers as to why some people get schizophrenia: No single gene or small number of genes explains much of the risk for illness. Instead, future studies must focus on larger numbers of interacting genes.
In a new paper published in PLOS ONE, researchers led by Bruce Cohen of Harvard Medical School and McLean Hospital report promising evidence on what one of those important groups of genes may be.
Previous studies of schizophrenia have shown abnormalities in the brain’s white matter—its wiring and insulation—but these studies could not definitively separate inherited from environmental causes. For this study, researchers used previously discovered anomalies to select likely assortments of genes that, as a group, might be highly determinative of the risk for schizophrenia. The choice of genes was based on convergent results of past studies conducted locally and around the world, and included genes that control the insulation of the nerve cells in the brain.
The results of this study strongly suggest that the abnormalities of wiring and insulation are substantially determined by genes.
“There is abundant evidence from our center and from other laboratories that this insulation is compromised in schizophrenia,” said Cohen, HMS Robertson-Steele Professor of Psychiatry and director of the Shervert Frazier Research Institute at McLean Hospital. “Based on this lead, we tested whether the genes required for the activities of the cells that make this insulation (oligodendrocytes) were associated with schizophrenia. In a primary analysis, followed by three separate means of confirmatory analysis, we found strong evidence that genes for oligodendrocytes, as a group, were indeed associated with schizophrenia.”
The findings suggest a concrete reason why insulation is disrupted in the brain in schizophrenia. This disruption in turn may explain why thinking is altered in schizophrenia: Nerve cells are unable to pass exact messages if they lack proper insulation.
Further, the findings show that the abnormality in insulation is at least in part genetically determined, rather than solely due to environmental factors such as years of treatment, different life activities or exposure to toxins.
Finally, the results identify a specific cell-level abnormality, in oligodendrocytes, in schizophrenia.
Similar findings, using different techniques, were recently reported by an independent group of investigators, working separately but contemporaneously with the authors of this study.
“Knowing that one of the pathways of risk for schizophrenia is in this set of genes and in these cells may help identify who is at risk and in what way they are at risk,” said Cohen. “The cells themselves will next be studied to define the problem and seek methods to prevent or reverse it. Thus, the findings can point us towards new ways to reduce the risk and burden of schizophrenia.”
Additional researchers from HMS, Harvard School of Public Health, McLean Hospital, Massachusetts General Hospital, The Broad Institute of MIT and Harvard, and the Cardiff University School of Medicine in Wales contributed to the study.
(Source: hms.harvard.edu)
How our brain networks: Research reveals white matter ‘scaffold’ of human brain
For the first time, neuroscientists have systematically identified the white matter “scaffold” of the human brain, the critical communications network that supports brain function.
Their work, published Feb. 11 in the open-source journal Frontiers in Human Neuroscience, has major implications for understanding brain injury and disease. By detailing the connections that have the greatest influence over all other connections, the researchers offer not only a landmark first map of core white matter pathways, but also show which connections may be most vulnerable to damage.
"We coined the term white matter ‘scaffold’ because this network defines the information architecture which supports brain function," said senior author John Darrell Van Horn of the USC Institute for Neuroimaging and Informatics and the Laboratory of Neuro Imaging at USC.
"While all connections in the brain have their importance, there are particular links which are the major players," Van Horn said.
Using MRI data from a large sample of 110 individuals, lead author Andrei Irimia, also of the USC Institute for Neuroimaging and Informatics, and Van Horn systematically simulated the effects of damaging each white matter pathway.
They found that the most important areas of white and gray matter don’t always overlap. Gray matter is the outermost portion of the brain containing the neurons where information is processed and stored. Past research has identified the areas of gray matter that are disproportionately affected by injury.
But the current study shows that the most vulnerable white matter pathways – the core “scaffolding” – are not necessarily just the connections among the most vulnerable areas of gray matter, helping explain why seemingly small brain injuries may have such devastating effects.
"Sometimes people experience a head injury which seems severe but from which they are able to recover. On the other hand, some people have a seemingly small injury which has very serious clinical effects," says Van Horn, associate professor of neurology at the Keck School of Medicine of USC. "This research helps us to better address clinical challenges such as traumatic brain injury and to determine what makes certain white matter pathways particularly vulnerable and important."
The researchers compare their brain imaging analysis to models used for understanding social networks. To get a sense of how the brain works, Irimia and Van Horn did not focus only on the most prominent gray matter nodes – which are akin to the individuals within a social network. Nor did they merely look at how connected those nodes are.
Rather, they also examined the strength of these white matter connections, i.e. which connections seemed to be particularly sensitive or to cause the greatest repercussions across the network when removed. Those connections which created the greatest changes form the network “scaffold.”
"Just as when you remove the internet connection to your computer you won’t get your email anymore, there are white matter pathways which result in large scale communication failures in the brain when damaged," Van Horn said.
When white matter pathways are damaged, brain areas served by those connections may wither or have their functions taken over by other brain regions, the researchers explain. Irimia and Van Horn’s research on core white matter connections is part of a worldwide scientific effort to map the 100 billion neurons and 1,000 trillion connections in the living human brain, led by the Human Connectome Project and the Laboratory of Neuro Imaging at USC.
Irimia notes that, “these new findings on the brain’s network scaffold help inform clinicians about the neurological impacts of brain diseases such as multiple sclerosis, Alzheimer’s disease, as well as major brain injury. Sports organizations, the military and the US government have considerable interest in understanding brain disorders, and our work contributes to that of other scientists in this exciting era for brain research.”
Your Brain Is Fine-Tuning Its Wiring Throughout Your Life
The white matter microstructure, the communication pathways of the brain, continues to develop/mature as one ages. Studies link age-related differences in white matter microstructure to specific cognitive abilities in childhood and adulthood.
Most prior studies, however, did not include individuals from the entire life span or evaluated a limited section of white matter tracts. This knowledge gap prompted a new study published this week in Biological Psychiatry.
Dr. Bart Peters, of the Zucker Hillside Hospital, and his colleagues investigated the relationship of age and neurocognitive performance to nine white matter tracts from childhood to late adulthood.
To accomplish this, they recruited 296 healthy volunteers who ranged from 8 to 68 years of age. The participants completed a comprehensive battery of tests designed to measure their cognitive functioning, including speed, attention, memory, and learning. They also underwent a non-invasive diffusion tensor imaging scan, a technology that allowed the researchers to create maps of the 9 major white matter tracts under investigation.
The combination of this data allowed them to identify the neurocognitive correlates of each white matter tract in relation to its unique aging pattern.
They found that, from childhood into early adulthood, differences in fractional anisotropy – a measure of connectivity – of the cingulum were associated with executive functioning, whereas fractional anisotropy of the inferior fronto-occipital fasciculus was associated with visual learning and global cognitive performance via speed of processing.
"Our study identified key brain circuits that develop during adolescence and young adulthood that are associated with the growth of learning, memory and planning abilities. These findings suggest that young people may not have full capacity of these functions until these connections have completed their normal trajectory of maturation beyond adolescence," explained Peters.
"Our brain is changing throughout our lives. These changes underlie the capacities that emerge and are refined through adulthood," commented Dr. John Krystal, Editor of Biological Psychiatry. “There are clues that the steps that we take to preserve our medical health and stimulate our minds also serve to further refine and maintain these connections. For good reasons, attending to brain health is increasingly a focus of healthy aging.”
In addition, many individuals diagnosed with psychiatric disorders suffer with neurocognitive dysfunction as part of their illness, which is particularly difficult to alleviate with currently available treatments. Studies such as this may help to identify specific brain circuits/pathways that could serve as potential targets for treatment interventions.