all Christopher A. Walsh stories

Middle Eastern families yield intriguing clues to autism

404132862 — Fri, 11 Jul 2008 12:27:58 -0400

Research involving large Middle Eastern families, sophisticated genetic analysis and groundbreaking neuroscience has implicated a half-dozen new genes in autism. More importantly, it strongly supports the emerging idea that autism stems from disruptions in the brain’s ability to form new connections in response to experience – consistent with autism’s onset during the first year of life, when many of these connections are normally made.

Slow reading in dyslexia tied to disorganized brain tracts

404132862 — Mon, 03 Dec 2007 15:29:31 -0500

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, Beth Israel Deaconess Medical Center (BIDMC), and the Harvard Graduate School of Education (HGSE) at the time the work was done. Their study, using the latest imaging methods, gives researchers a glimpse of what may go wrong in the structure of some dyslexic readers’ brains that makes it difficult to integrate the information needed for rapid, “automatic” reading.

Gene clue to brain asymmetry revealed on right side

70652986 — Mon, 26 Mar 2007 06:20:47 -0400

Although many assumed that the asymmetry-producing genes, when found, would be more highly expressed on the left side of the brain than the right, Sun Tao, Christopher A. Walsh, and their colleagues found otherwise. One gene, LMO4, that showed the most consistent difference was much more highly expressed on the right.

The researchers found that mouse brains also express the LMO4 gene asymmetrically. But the asymmetry was unpredictable. Some mice expressed LMO4 at higher levels on the right, others on the left.

Inspired by the fact that a small percentage of humans also have a reversed asymmetry, Sun, an HMS research fellow in neurology at Beth Israel Deaconess, and Walsh hypothesized that slight differences between the hemispheres could be used to establish dominance in language.

Sun started by collecting samples of the right and left perisylvian cortices of human brains. He then compared their gene expression patterns. One gene, LMO4, exhibited consistent left- right variation in expression at two important stages, 12 and 14 weeks. It was only when the researchers approached the perisylvian cortex that the right-left difference started appearing.

Although LMO4's role is unclear, researchers believe it may be involved in selecting one type of connection over another. If so, it could be receiving instructions from earlier genes. "We want to look at these earlier stages to find out what the genes are that guide the patterning," said Sun.

Newly identified gene linked to brain development

70652986 — Mon, 26 Mar 2007 07:10:26 -0400

Bilateral frontoparietal polymicrogyria (BFPP) is a recessive genetic disorder resulting in severely abnormal architecture of the brain's frontal lobes, as well as milder involvement of parietal and posterior parts of the cerebral cortex, which is "the part of the brain that distinguishes humans from other species," says the study's senior author, Christopher A. Walsh, M.D., Ph.D., a Howard Hughes Medical Institute investigator at BIDMC's Neurogenetics Division and Bullard Professor of Neurology at Harvard Medical School.

In this new study, lead author Xianhua Piao M.D., Ph.D., and colleagues identified the BFPP gene as GPR56, which plays an especially important role in the frontal portions of the cortex.

Walsh's laboratory identifies genes that disrupt the normal cerebral cortex development, thereby helping to define the clinical syndromes of certain human developmental disorders. These new findings, he says, suggest that GPR56 may have been a key target in the evolution of the cerebral cortex.

"Being able to access the complete sequence of the human genome has allowed us to identify increasing numbers of genes that are required for cortical development," he adds. "Although these genes cause mental retardation, by studying the biological function of their gene products we also gain insight into the normal development and function of the human brain."

Genes found that regulate brain size

70652986 — Mon, 26 Mar 2007 05:23:57 -0400

A gene that builds bigger brains, called beta-catenin, was discovered in the laboratory of Christopher A. Walsh, Bullard Professor of Neurology at Harvard Medical School. Researchers there engineered increased activity into the beta-catenin gene in mice, and the mice brains grew to almost twice the usual size. Not only that, but the cerebral cortex, seat of intelligence and language, became more humanlike. Walsh and his colleagues, working with C. Geoffrey Woods at St. James University Hospital in Leeds, England, also identified a gene known as ASPM, mutations of which are a major cause of inherited microcephaly. Finding ASPM opens the way to genetic counseling and prenatal diagnoses for families at high risk for the disease.

Why the brains of humans are bigger

70652986 — Mon, 26 Mar 2007 05:23:14 -0400

The largest structure in the brain, the cerebral cortex is the headquarters of our intellect -- often referred to as "gray matter." The large surface area of the cortex houses two-thirds of the brain's 100 billion neurons in a thin layer, only slightly thicker than the peel of an orange. In order for this expanded surface area to fit within the confines of the human skull, the cortex folds in on itself, resulting in a series of ridges and grooves that give the brain its "wrinkled" appearance. This characteristic is unique to humans. "This study looked at how the cerebral cortex develops and the role of the beta catenin protein in cortical growth," explains senior author Christopher A. Walsh, a neurogeneticist at Beth Israel Deaconess Medical Center who has been studying cortical development and its role in mental retardation and epilepsy for nearly 10 years. Walsh, who is also the Bullard Professor of Neurology at the Medical School, and Anjen Chenn, a research fellow in Walsh's laboratory and a pathologist at Brigham and Women's Hospital, worked together on the investigation into how and why the human cortex grows so large.

"Commoner" in brain crowns the cortex

70652986 — Mon, 26 Mar 2007 05:17:03 -0400

With its role in higher cognitive functions, the cortex represents a significant evolutionary development in mammals, culminating in the enlarged hemispheres of humans and other primates. In the development of this crowning structure, neurons are guided by factors that are both genetic and environmental. A research team led by Christopher A. Walsh, the Bullard professor of neurology at Beth Israel Deaconess Medical Center, recently discovered that one gene in particular is necessary to form the cortex, serving as a selective switch for development.