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Thursday, February 6th, 2014
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| 5:00a |
Vision is key to spatial skills
Try to conjure a mental image of your kitchen, or imagine the route that you take to work every day. For most people, this comes so naturally that we think nothing of it, but for neuroscientists, there is still much to learn about how the brain develops this critical skill, known as spatial imagery.
Sensory information from the eyes, ears, and sense of touch all contribute to our ability to imagine spatial structures, but questions remain about the influence of each sensory system. A new study from MIT neuroscientists suggests that visual input plays a special role in developing these skills, particularly for more complex tasks.
By studying children in India who were born blind but whose blindness could be treated, the researchers found that the children’s ability to perform more complex spatial imagery tasks improved markedly following surgery that restored their sight.
“Just four months of vision seems to have a significant impact on spatial imagery skills,” says Pawan Sinha, an MIT professor of brain and cognitive sciences and senior author of the paper. “That seems to be consistent with the greater richness of spatial information that vision provides. With audition and touch we get a coarser sense of the environment. With vision we have a much more fine-grained appreciation of the environment.”
The study, which appeared in a recent issue of the journal Psychological Science, grew out of Project Prakash, a charitable effort Sinha launched to identify and treat children in India suffering from curable forms of blindness, such as cataracts or corneal scarring.
Tapan Gandhi, a postdoc in Sinha’s lab, is the paper’s lead author; Suma Ganesh, an ophthalmologist at Dr. Shroff’s Charity Eye Hospital in New Delhi, is also an author.
The role of vision
Previous studies of spatial imagery skills among blind individuals have offered conflicting findings.
“Blind individuals, even those who have been blind from birth, are not entirely at a loss for spatial abilities. Blind individuals can navigate through the environment, and that must tap into some imagery abilities,” Gandhi says. “However, some studies had indicated that blind individuals might be a little worse off relative to their sighted counterparts.”
These differences might result from lack of visual input, but could also stem from the more limited opportunities that blind people have to interact with their environment. “There’s still a question mark about the role of vision, despite the previous results,” Sinha says.
Studying the Project Prakash patients offered a unique opportunity to try to answer this question. But first, the researchers studied two other groups of children — 30 children whose blindness was not treatable, and 30 normally sighted children.
To test their spatial imagery skills, children were first given a pegboard with a grid of pegs arranged 2 by 2, 3 by 3, or 4 by 4. Sighted children were blindfolded during the task. After a child became familiar with the pegboard, it was taken away and the experimenter asked him or her to mentally trace a verbally described path (e.g. “right, up, right, up, left, right”) along the board, beginning from the lower left peg.
The researchers then returned the pegboard and asked the child to locate the final position of the imagined path. When the path was shorter and the grid smaller, blind children performed just as well on this task as the sighted children. However, as the path became longer and grid became larger, the blind children’s performance declined in comparison with the sighted children’s.
In their next set of tests, with 10 children treated through Project Prakash, the researchers investigated whether the onset of vision would improve performance.
A few days before their surgery, these children performed the same as the blind children previously tested in the pegboard task. The researchers then tested the children again, an average of four months after their operation. In these follow-up tests, the children performed much better on the more complex tasks — in fact, at the same level as normally sighted children.
“When they didn’t have visual experience, they were still able to perform very simple tasks, but not very complex tasks. But when they received sight after the surgery, they developed this ability very fast,” Gandhi says.
Albert Yonas, a professor of child psychology at the University of Minnesota, says the work takes a sophisticated approach to investigating vision’s role in spatial imagery. “One could ask a simple question, ‘Does visual experience influence imagery or not?’ Rather, this work varies the difficulty of the task and finds both no effects when representational demands are minimal and a large effect of experience when the task requires a flexible and extensive spatial representation,” says Yonas, who was not part of the research team.
Spatial representations
The findings suggest that either there is no strictly defined time window for vision to contribute to spatial imagery ability, or that if there is a “critical period,” it extends at least into late adolescence, Sinha says.
The study also raises questions about how visual input affects the development of spatial imagery abilities, Sinha says. One major question is whether visual input changes the nature of the spatial representations used by blind children.
“The spatial information they develop about the environment through their tactile system could be qualitatively different from the spatial structures they develop through the use of vision,” Sinha says. “Or, it could be the case that vision simply elaborates the representations that they already possess.”
The researchers hope to answer this question by using functional magnetic resonance imaging (fMRI) to scan children’s brains as they perform spatial imagery tasks before and after being treated for blindness. Gandhi and Sinha are also interested in exploring whether there is any way to enhance spatial imagery abilities in blind children whose blindness is not treatable.
The study was funded by the James McDonnell Foundation and the National Eye Institute. | | 5:00a |
A microchip for metastasis
Nearly 70 percent of patients with advanced breast cancer experience skeletal metastasis, in which cancer cells migrate from a primary tumor into bone — a painful development that can cause fractures and spinal compression. While scientists are attempting to better understand metastasis in general, not much is known about how and why certain cancers spread to specific organs, such as bone, liver, and lungs.
Now researchers from MIT, Italy, and South Korea have developed a three-dimensional microfluidic platform that mimics the spread of breast cancer cells into a bonelike environment.
The microchip — slightly larger than a dime — contains several channels in which the researchers grew endothelial cells and bone cells to mimic a blood vessel and bone side-by-side. They then injected a highly metastatic line of breast cancer cells into the fabricated blood vessel.
Twenty-four hours later, the team observed that twice as many cancer cells had made their way through the vessel wall and into the bonelike environment than had migrated into a simple collagen-gel matrix. Moreover, the cells that made it through the vessel lining and into the bonelike setting formed microclusters of up to 60 cancer cells by the experiment’s fifth day.
“You can see how rapidly they are growing,” says Jessie Jeon, a graduate student in mechanical engineering. “We only waited until day five, but if we had gone longer, [the size of the clusters] would have been overwhelming.”
The team also identified two molecules that appear to encourage cancer cells to metastasize: CXCL5, a protein ligand secreted by bone cells, and CXCR2, a receptor protein on cancer cells that binds to the ligand. The preliminary results suggest that these molecules may be potential targets to reduce the spread of cancer.
Jeon says the experiments demonstrate that the microchip may be used in the future to test drugs that might stem metastasis, and also as a platform for studying cancer’s spread to other organs.
She and her colleagues, including Roger Kamm, the Cecil and Ida Green Distinguished Professor of Mechanical and Biological Engineering at MIT, have outlined the results of their experiments in the journal Biomaterials.
“Currently, we don't understand why certain cancers preferentially metastasize to specific organs,” Kamm says. “An example is that breast cancer will form metastatic tumors in bone, but not, for example, muscle. Why is this, and what factors determine it? We can use our model system both to understand this selectivity, and also to screen for drugs that might prevent it.”
Through a wall and into bone
The process by which cancer cells form secondary tumors requires the cells to first survive a journey through the circulatory system. These migrating cells attach to a blood vessel’s inner lining, and ultimately squeeze through to the surrounding tissue — a process called extravasation, which Kamm’s research group modeled last fall using a novel microfluidic platform.
Now the group is looking to the next step in metastasis: the stage at which a cancer cell invades a specific organ. In particular, the researchers designed a microchip in which they could observe interactions between specific cancer cells and a receptive, organlike environment. They chose to work first with osteo-differentiated cells, as bone is a major target of metastasizing breast cancer cells.
The group collected marrow-derived stem cells from patients undergoing hip surgery, and allowed the cells to naturally differentiate into bone cells. They also obtained commercially available endothelial cells, and lined one channel in the microchip with endothelial cells to mimic a blood vessel wall. They filled another channel with differentiated bone cells to form a bonelike matrix, and finally injected human breast cancer cells into the channel containing endothelial cells.
Jeon and her colleagues captured images of the metastatic process: Cancer cells pushed through the vessel wall, spread into the bonelike environment, and clustered deep in the bone matrix to form tiny tumors.
In particular, they found that twice as many cancer cells spread to the bonelike environment as to a standard collagen matrix; these also spread deeper into the bone matrix, forming microclusters of up to 60 cells after five days.
To see what molecular signals might explain the difference in metastatic rate, the team focused on CXCL5 and CXCR2. While these two proteins are known to have a role in metastasis, it’s not clear whether they promote it in specific organs.
The researchers incubated cancer cells with an antibody that blocked CXCR2, and found that these cells were less able to break through the blood vessel lining. They also tried injecting CXCL5 into a collagen-gel matrix without bone cells, and found that the ligand-seeded environment encouraged breast cancer cells to invade. The results suggest these two proteins may be targets for preventing or mitigating cancer metastasis not just in bone, but in other organs as well.
“The beauty of this system lies in its simplicity and elegance,” says Muhammad Zaman, an associate professor of biological engineering at Boston University who was not involved in the research. “I believe that this microfluidic system will be easy to scale to study processes that are important yet have been too difficult to quantify. Overall, I think this is a major breakthrough to understand complex processes, underscore the importance of mechanics and identify novel pathways for treatment.”
The team plans to explore cancer metastasis in other organs, such as muscle — an organ in which cancer cells do not easily spread.
“There are some organs known to be more or less metastatic, and if we can add two different organ types, we can see what kind of differences there are,” Jeon says.
Kamm adds that in the future, such a platform may be used in personalized medicine to determine the best cancer therapy for a given patient.
“One might envision using cells from the cancer patient to produce models of different organs, then using these models to determine the optimal therapy from a variety of available drugs,” Kamm says.
This research was supported by the National Cancer Institute and the Italian Ministry of Health.
| | 7:00p |
Theorists predict new forms of exotic insulating materials
Topological insulators — materials whose surfaces can freely conduct electrons even though their interiors are electrical insulators — have been of great interest to physicists in recent years because of unusual properties that may provide insights into quantum physics. But most analysis of such materials has had to rely on highly simplified models.
Now, a team of researchers at MIT has performed a more detailed analysis that hints at the existence of six new kinds of topological insulators. The work also predicts the materials’ physical properties in sufficient detail that it should be possible to identify them unambiguously if they are produced in the lab, the scientists say.
The new findings are reported this week in the journal Science by MIT professor of physics Senthil Todadri, graduate student Chong Wang, and Andrew Potter, a former MIT graduate student who is now a postdoc at the University of California at Berkeley.
“In contrast to conventional insulators, the surface of the topological insulators harbors exotic physics that are interesting both for fundamental physics, and possibly for applications,” Senthil says. But attempts to study the properties of these materials have “relied on a highly simplified model in which the electrons inside the solid are treated as though they did not interact with each other.” New analytical tools applied by the MIT team now reveal “that there are six, and only six, new kinds of topological insulators that require strong electron-electron interactions.”
“The surface of a three-dimensional material is two-dimensional,” Senthil says — which explains why the electrical behavior of the surface of a topological insulator is so different from that of the interior. But, he adds, “The kind of two-dimensional physics that emerges [on these surfaces] can never be in a two-dimensional material. There has to be something inside, otherwise this physics will never occur. That’s what’s exciting about these materials,” which reveal processes that don’t show up in other ways.
In fact, Senthil says, this new work based on analysis of such surface phenomena shows that some previous predictions of phenomena in two-dimensional materials “cannot be right.”
Since this is a new finding, he says, it is too soon to say what applications these new topological insulators might have. But the analysis provides details on predicted properties that should allow experimentalists to begin to understand the behavior of these exotic states of matter.
“If they exist, we know how to detect them,” Senthil says of these new phases. “And we know that they can exist.” What this research doesn’t yet show, however, is what these new topological insulators’ composition might be, or how to go about creating them.
The next step, he says, is to try to predict “what compositions might lead to” these newly predicted phases of topological insulators. “It’s an open question now that we need to attack.”
Joel Moore, a professor of physics at the University of California at Berkeley, says, “I think it is a very insightful piece of work. It is less about a very complicated calculation than about thinking deeply and abstractly.” While much work remains to be done to find or create such materials, he says, “this work provides some clear guidance,” revealing that the number of possible states “is remarkably small” and that understanding their properties should not be as complicated as might have been expected.
The research was supported by the U.S. Department of Energy, the National Science Foundation, and the Simons Foundation. |
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