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Posts Tagged ‘white matter

Brain Less Coordinated With Age, Even In The Absence Of Disease

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Some brain systems become less coordinated with age even in the absence of Alzheimer’s disease, according to a new study from Harvard University. The results help to explain why advanced age is often accompanied by a loss of mental agility, even in an otherwise healthy individual.

The study was led by Jessica Andrews-Hanna, a doctoral candidate in the Department of Psychology in the Faculty of Arts and Sciences at Harvard.

“This research helps us to understand how and why our minds change as we get older, and why some individuals remain sharp into their 90s, while others’ mental abilities decline as they age,” says Andrews-Hanna. “One of the reasons for loss of mental ability may be that these systems in the brain are no longer in sync with one another.”

Previous studies have focused on the specific structures and functions within the brain, and how their deterioration might lead to decreased cognitive abilities. However, this study examined the way that large-scale brain systems that support higher-level cognition correlate and communicate across the brain, and found that in older adults these systems are not in sync. In particular, widely separated systems from the front to the back of the brain were less correlated.

The human brain can be divided into major functional regions, each responsible for different kinds of “applications,” such as memory, sensory input and processing, executive function or even one’s own internal musing. The functional regions of the brain are linked by a network of white matter conduits. These communication channels help the brain coordinate and share information from the brain’s different regions. White matter is the tissue through which messages pass from different regions of the brain.

Scientists have known that white matter degrades with age, but they did not understand how that decline contributes to the degradation of the large-scale systems that govern cognition.

“The crosstalk between the different parts of the brain is like a conference call,” said Jessica Andrews-Hanna, a graduate student in Buckner’s lab and the lead author of the study. “We were eavesdropping on this crosstalk and we looked at how activity in one region of the brain correlates with another.”

The researchers studied 55 older adults, approximately age 60 and over, and 38 younger adults, approximately age 35 and younger. They used a neuroimaging technique called fMRI to obtain a picture of activity in the brain. The results showed that among the younger people, brain systems were largely in sync with one another, while this was not the case with the older individuals.

Among the older individuals, some of the subjects’ brains systems were correlated, and older individuals that performed better on psychometric tests were more likely to have brain systems that were in sync. These psychometric tests, administered in addition to the fMRI scanning, measured memory ability, processing speed and executive function.

Among older individuals whose brain systems did not correlate, all of the systems were not affected in the same way. Different systems process different kinds of information, including the attention system, used to pay attention, and the default system, used when the mind is wandering. The default system was most severely disrupted with age. Some systems do remain intact; for example, the visual system was very well preserved. The study also showed that the white matter of the brain, which connects the different regions of the brain, begins to lose integrity with age.

One of the challenges to studying the aging brain is that the early signs of Alzheimer’s disease are very subtle, and it is difficult to distinguish between the early stages of Alzheimer’s disease and normal aging. In order to ensure that the researchers were only looking at healthy aging brains, the researchers used a PET scanning process to identify the presence of amyloid, a chemical present in individuals with Alzheimer’s. When the presence of this chemical was detected, individuals were not included in the study. In this way, the researchers ensured that they were looking at a healthy aging brain.

“Understanding why we lose cognitive function as we age may help us to prolong our mental abilities later in life,” says Buckner. “The results of this study help us to understand how the aging brain differs from the brain of a younger individual.”

This research was published in the Dec. 6 issue of Neuron. Other researchers involved in this study include Justin Vincent, a graduate student in the Department of Psychology at Harvard and Randy Buckner, Harvard professor of psychology and an investigator with the Howard Hughes Medical Institute. Co-authors also include Andrew Snyder, Denise Head and Marcus Raichle of Washington University in St. Louis and Cindy Lustig of the University of Michigan.

The research was funded by the National Institutes of Health, the Alzheimer’s Association, and the Howard Hughes Medical Institute.

Neuron. 2007 Dec 6;56(5):924-35.

Disruption of large-scale brain systems in advanced aging.

Andrews-Hanna JR, Snyder AZ, Vincent JL, Lustig C, Head D, Raichle ME, Buckner RL.

Department of Psychology, Center for Brain Science, Harvard University, Cambridge, MA 02138, USA; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA 02129, USA.

Cognitive decline is commonly observed in advanced aging even in the absence of disease. Here we explore the possibility that normal aging is accompanied by disruptive alterations in the coordination of large-scale brain systems that support high-level cognition. In 93 adults aged 18 to 93, we demonstrate that aging is characterized by marked reductions in normally present functional correlations within two higher-order brain systems. Anterior to posterior components within the default network were most severely disrupted with age. Furthermore, correlation reductions were severe in older adults free from Alzheimer’s disease (AD) pathology as determined by amyloid imaging, suggesting that functional disruptions were not the result of AD. Instead, reduced correlations were associated with disruptions in white matter integrity and poor cognitive performance across a range of domains. These results suggest that cognitive decline in normal aging arises from functional disruption in the coordination of large-scale brain systems that support cognition.

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Written by huehueteotl

December 7, 2007 at 1:52 pm

Slow Reading In Dyslexia Tied To Disorganized Brain Tracts

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Dyslexia marked by poor reading fluency — slow and choppy reading — may be caused by disorganized, meandering tracts of nerve fibers in the brain, according to researchers at Children’s Hospital Boston and Beth Israel Deaconess Medical Center (BIDMC). The study, using the latest imaging methods, gives researchers a glimpse of what may go wrong in the structure of some dyslexic readers’ brains, making it difficult to integrate the information needed for rapid, “automatic” reading.

In a normal brain (left), white matter (light gray) is in the interior, and gray matter (dark gray) is mostly on the surface. In patients with periventricular nodular heterotopia (right), clumps of gray matter, called nodules (red arrows), appear deep within the brain, instead of on the surface. (Credit: Bernard Chang, Beth Israel Deaconess Medical Center)

The study was led by Christopher Walsh, MD, PhD, chief of the Division of Genetics at Children’s Hospital Boston, and Bernard Chang, MD, a neurologist at BIDMC.
“We looked at dyslexia caused by a particular genetic disorder, but what we found could have implications for understanding the causes of dyslexia in other populations as well,” says Walsh, who is also a Howard Hughes Medical Institute investigator at BIDMC.

Dyslexia, which affects 5 to 15 percent of all children, has different forms. Subjects in the study had reading problems caused by a rare genetic disorder known as periventricular nodular heterotopia, or PNH. Although their intelligence is normal, people with PNH have trouble reading fluently, or smoothly, lacking the rapid processing necessary for this aspect of reading.

The genetic mutation that causes PNH disrupts brain structure. In a normal brain, much of the gray matter (consisting mostly of nerve cells) appears on the brain’s surface, while white matter (consisting mostly of nerve fibers or “wiring” connecting areas of gray matter) runs deeper in the brain. In PNH, nodules of gray matter sit deep in the brain’s core, in the white matter, having failed to migrate out to the surface as the brain was developing.

To learn more about how these developmental changes in the brain might lead to reading problems, the researchers tested cognitive skills needed for reading in 10 patients with PNH, 10 individuals with dyslexia without neurological problems, and 10 normal readers. They used a specialized form of MRI called diffusion tensor imaging to look at the structure of the white matter in the brain.

In PNH patients, unlike in normal readers, white matter fibers took circuitous routes around the misplaced gray matter, and in some cases, didn’t organize into uniform bundles, which could leave regions of gray matter poorly connected. Importantly, the more disorganized the PNH patients’ white matter, the less fluent their reading.

While other studies have found disorganized white matter in the general population of people with dyslexia, these individuals often struggle with several aspects of reading, making it “hard to know exactly what the role of white-matter integrity is in isolation,” says Chang. By demonstrating white-matter problems in PNH patients, who have an isolated reading fluency problem, and correlating that with reading fluency scores, the researchers were able to conclude that white-matter integrity and organization may be the structural basis in the brain for reading fluency.

“This makes sense,” says Chang. “When we read, we need to take in information visually, hook it up with our inner dictionary of what letters and words mean, and when we’re reading aloud, connect that with the region that gives us our ability to speak.” For smooth, automatic reading, “the white matter is there to connect different regions of gray matter and allow them to function seamlessly.” When reading fluency is the primary problem, “it may be that the areas of the brain that are important for reading are not connected efficiently,” says Chang.

Most people with dyslexia who have trouble reading fluently don’t have misplaced gray matter or PNH. But Walsh and Chang believe that disorganized white matter could similarly alter brain function in both groups. Their next study will examine how faulty white-matter connections alter brain patterns, comparing brain activation during reading in PNH patients and in dyslexic readers with poor fluency, who do not have PNH.

“Our findings suggest that white matter integrity plays a critical role in reading fluency and that defects in white matter serve as the structural basis for the type of dyslexia we see in this brain malformation,” said the study’s lead author Bernard S. Chang, MD, with Harvard Medical School in Boston, and member of the American Academy of Neurology. “Our work highlights the importance of studying white matter structure in order to understand cognitive problems and learning disabilities more fully.”

Pinpointing the brain structures responsible for fluent reading may eventually help researchers and educational specialists develop and use techniques that help improve the automatic nature of reading in children and adults with these kinds of difficulties, the researchers note.

NEUROLOGY 2007;69:2146-2154

A structural basis for reading fluency: White matter defects in a genetic brain malformation

B. S. Chang, MD, T. Katzir, PhD, T. Liu, PhD, K. Corriveau, MEd, M. Barzillai, MEd, K. A. Apse, ScM, A. Bodell, MS, D. Hackney, MD, D. Alsop, PhD, S. Wong, PhD and C. A. Walsh, MD, PhD

 Background: Multiple lines of evidence have suggested that developmental dyslexia may be associated with abnormalities of neuronal migration or axonal connectivity. In patients with periventricular nodular heterotopia—a rare genetic brain malformation characterized by misplaced nodules of gray matter along the lateral ventricles—a specific and unexpected reading disability is present, despite normal intelligence. We sought to investigate the cognitive and structural brain bases of this phenomenon.

Methods: Ten adult subjects with heterotopia, 10 with dyslexia, and 10 normal controls were evaluated, using a battery of neuropsychometric measures. White matter integrity and fiber tract organization were examined in six heterotopia subjects, using diffusion tensor imaging methods.

Results: Subjects with heterotopia and those with developmental dyslexia shared a common behavioral profile, with specific deficits in reading fluency. Individuals with dyslexia seemed to have a more prominent phonological impairment than heterotopia subjects. Periventricular nodular heterotopia was associated with specific, focal disruptions in white matter microstructure and organization in the vicinity of gray matter nodules. The degree of white matter integrity correlated with reading fluency in this population.

Conclusions: We demonstrate that a genetic disorder of gray matter heterotopia shares behavioral characteristics with developmental dyslexia, and that focal white matter defects in this disorder may serve as the structural brain basis of this phenomenon. Our findings represent a potential model for the use of developmental brain malformations in the investigation of abnormal cognitive function.see also:

What Is Dyslexia?

Written by huehueteotl

December 4, 2007 at 12:05 pm