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News Article | November 23, 2016
Site: www.eurekalert.org

Groups of brain regions with coordinated activity are consistent for individuals, but shrink with age Groups of brain regions that synchronize their activity during memory tasks become smaller and more numerous as people age, according to a study published in PLOS Computational Biology. Typically, research on brain activity relies on average brain measurements across entire groups of people. In a new study, Elizabeth Davison of Princeton University, New Jersey, and colleagues describe a novel method to characterize and compare the brain dynamics of individual people. The researchers used functional magnetic resonance imaging (fMRI) to record healthy people's brain activity during memory tasks, attention tasks, and at rest. For each person, fMRI data was recast as a network composed of brain regions and the connections between them. The scientists then use this network to measure how closely different groups of connections changed together over time. They found that, regardless of whether a person is using memory, directing attention, or resting, the number of synchronous groups of connections within one brain is consistent for that person. However, between people, these numbers vary dramatically. During memory specifically, variations between people are closely linked to age. Younger participants have only a few large synchronous groups that link nearly the entire brain in coordinated activity, while older participants show progressively more and smaller groups of connections, indicating loss of cohesive brain activity--even in the absence of memory impairment. "This method elegantly captures important differences between individual brains, which are often complex and difficult to describe," Davison says. "The resulting tools show promise for understanding how different brain characteristics are related to behavior, health, and disease." Future work will investigate how to use individual brain signatures to differentiate between healthily aging brains and brains with age-related impairments. In your coverage please use this URL to provide access to the freely available article in PLOS Computational Biology: http://journals. Citation: Davison EN, Turner BO, Schlesinger KJ, Miller MB, Grafton ST, Bassett DS, et al. (2016) Individual Differences in Dynamic Functional Brain Connectivity across the Human Lifespan. PLoS Comput Biol 12(11): e1005178. doi:10.1371/journal.pcbi.1005178 Funding: This work was supported by the David and Lucile Packard Foundation and the Institute for Collaborative Biotechnologies through grant W911NF-09-0001 from the U.S. Army Research Office. KJS was supported by the National Science Foundation Graduate Research Fellowship Program under Grant No. DGE-1144085. END was supported by the National Science Foundation Graduate Research Fellowship Program under Grant No. DGE-1656466 and the Francis Robbins Upton Fellowship in Engineering. END and KJS were additionally supported by the Worster Fellowship. DSB acknowledges support from the John D. and Catherine T. MacArthur Foundation, the Army Research Laboratory and the Army Research Office through contract numbers W911NF-10-2-0022 and W911NF-14-1-0679, the National Institute of Mental Health (2-R01-DC- 009209-11), the National Institute of Child Health and Human Development (1R01HD086888-01), the Office of Naval Research, and the National Science Foundation (#BCS-1441502, #BCS-1430087, and #PHY-1554488). The content of the information does not necessarily reflect the position or the policy of the Government, and no official endorsement should be inferred. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist.


News Article | November 28, 2016
Site: www.eurekalert.org

Studies of brain activity typically draw their findings from measurement averages across entire groups of subjects. But new research out of UC Santa Barbara that highlights a novel method of characterizing and comparing the brain dynamics in individuals may signal a shift in that approach. While UCSB scientists have demonstrated that the groups of regions of the brain that synchronize their activity during memory-related tasks get smaller and more numerous with age, the number of connections is as individual as the study participants. The research findings appear in the journal PLOS Computational Biology. "We found that the way our brain organizes its communications changes as we age," said co-author Kimberly Schlesinger, a Ph.D. student at UCSB. "Even though we saw different patterns of brain activity in older people, we didn't see any changes in memory performance. This suggests that while older people have less synchronized communication across their entire brains, they may be compensating for this by using different strategies to successfully remember things." The scientists used functional magnetic resonance imaging (fMRI) to record healthy people's brain activity during memory tasks, attention tasks and periods of rest. For each person, fMRI data was recast as a network composed of brain regions and the connections among them. The investigators then measured how closely different groups of connections changed together over time. They found that regardless of whether a person is using memory, directing attention or resting, the number of synchronous groups of connections within one brain is consistent for that person. However, among multiple people, these numbers vary dramatically. Specifically during memory, variations among people are closely linked to age. Younger participants had only a few large synchronous groups that link nearly the entire brain in coordinated activity, while older participants showed progressively more and smaller groups of connections, indicating loss of cohesive brain activity -- even in the absence of memory impairment. "This method elegantly captures important differences between individual brains, which are often complex and difficult to describe," said Elizabeth Davison, who initiated the work as an undergraduate at UCSB, where Schlesinger served as her mentor. Davison is now a graduate student at Princeton University. "The resulting tools show promise for understanding how different brain characteristics are related to behavior, health and disease." The research originated from the Worster Summer Research Fellowship in UCSB's Department of Physics. Other UCSB members of the project team included physics professor Jean Carlson, neuroscientist Scott Grafton and then-postdoctoral scholar Danielle Bassett, now an assistant professor at the University of Pennsylvania. Future work will investigate how to use individual brain signatures to differentiate between brains that are healthily aging and those with age-related impairments. This study was supported by the David and Lucile Packard Foundation and the Institute for Collaborative Biotechnologies through a grant from the U.S. Army Research Office. Schlesinger was supported by the National Science Foundation Graduate Research Fellowship Program and by the Worster Summer Research Fellowship.


News Article | October 23, 2015
Site: news.mit.edu

MIT chemical engineers have designed tiny particles that can “steer” themselves along preprogrammed trajectories and align themselves to flow through the center of a microchannel, making it possible to control the particles’ flow through microfluidic devices without applying any external forces. Such particles could make it more feasible to design lab-on-a-chip devices, which hold potential as portable diagnostic devices for cancer and other diseases. These devices consist of microfluidic channels engraved on tiny chips, but current versions usually require a great deal of extra instrumentation attached to the chip, limiting their portability. Much of that extra instrumentation is needed to keep the particles flowing single file through the center of the channel, where they can be analyzed. This can be done by applying a magnetic or electric field, or by flowing two streams of liquid along the outer edges of the channel, forcing the particles to stay in the center. The new MIT approach, described in Nature Communications, requires no external forces and takes advantage of hydrodynamic principles that can be exploited simply by altering the shapes of the particles. Lead authors of the paper are Burak Eral, an MIT postdoc, and William Uspal, who recently received a PhD in physics from MIT. Patrick Doyle, the Singapore Research Professor of Chemical Engineering at MIT, is the senior author of the paper. The work builds on previous research showing that when a particle is confined in a narrow channel, it has strong hydrodynamic interactions with both the confining walls and any neighboring particles. These interactions, which originate from how particles perturb the surrounding fluid, are powerful enough that they can be used to control the particles’ trajectory as they flow through the channel. The MIT researchers realized that they could manipulate these interactions by altering the particles’ symmetry. Each of their particles is shaped like a dumbbell, but with a different-size disc at each end. When these asymmetrical particles flow through a narrow channel, the larger disc encounters more resistance, or drag, forcing the particle to rotate until the larger disc is lagging behind. The asymmetrical particles stay in this slanted orientation as they flow. Because of this slanted orientation, the particles not only move forward, in the direction of the flow, they also drift toward one side of the channel. As a particle approaches the wall, the perturbation it creates in the fluid is reflected back by the wall, just as waves in a pool reflect from its wall. This reflection forces the particle to flip its orientation and move toward the center of the channel. Slightly asymmetrical particles will overshoot the center and move toward the other wall, then come back toward the center again until they gradually achieve a straight path. Very asymmetrical particles will approach the center without crossing it, but very slowly. But with just the right amount of asymmetry, a particle will move directly to the centerline in the shortest possible time. “Now that we understand how the asymmetry plays a role, we can tune it to what we want. If you want to focus particles in a given position, you can achieve that by a fundamental understanding of these hydrodynamic interactions,” Eral says. “The paper convincingly shown that shape matters, and swarms can be redirected provided that shapes are well designed,” says Patrick Tabeling, a professor at the École Supérieure de Physique et de Chimie Industrielles in Paris, who was not part of the research team. “The new and quite sophisticated mechanism … may open new routes for manipulating particles and cells in an elegant manner.” In 2006, Doyle’s lab developed a way to create huge batches of identical particles made of hydrogel, a spongy polymer. To create these particles, each thinner than a human hair, the researchers shine ultraviolet light through a mask onto a stream of flowing building blocks, or oligomers. Wherever the light strikes, solid polymeric particles are formed in the shape of the mask, in a process called photopolymerization. During this process, the researchers can also load a fluorescent probe such as an antibody at one end of the dumbbell. The other end is stamped with a barcode — a pattern of dots that reveals the particle’s target molecule. This type of particle can be useful for diagnosing cancer and other diseases, following customization to detect proteins or DNA sequences in blood samples that can be signs of disease. Using a cytometer, scientists can read the fluorescent signal as the particles flow by in single file. “Self-steering particles could lead to simplified flow scanners for point-of-care devices, and also provide a new toolkit from which one can develop other novel bioassays,” Doyle says. The research was funded by the National Science Foundation, Novartis, and the Institute for Collaborative Biotechnologies through the U.S. Army Research Office.


Xiao Y.,Institute for Polymers and Organic Solids | Xiao Y.,Institute for Collaborative Biotechnologies | Dane K.Y.,Institute for Collaborative Biotechnologies | Uzawa T.,Institute for Collaborative Biotechnologies | And 8 more authors.
Journal of the American Chemical Society | Year: 2010

Although the telomeric repeat amplification protocol (TRAP) has served as a powerful assay for detecting telomerase activity, its use has been significantly limited when performed directly in complex, interferant-laced samples. In this work, we report a modification of the TRAP assay that allows the detection of high-fidelity amplification of telomerase products directly from concentrated cell lysates. Briefly, we covalently attached 12 nm gold nanoparticles (AuNPs) to the telomere strand (TS) primer, which is used as a substrate for telomerase elongation. These TS-modified AuNPs significantly reduce polymerase chain reaction (PCR) artifacts (such as primer dimers) and improve the yield of amplified telomerase products relative to the traditional TRAP assay when amplification is performed in concentrated cell lysates. Specifically, because the TS-modified AuNPs eliminate most of the primer-dimer artifacts normally visible at the same position as the shortest amplified telomerase PCR product apparent on agarose gels, the AuNP-modified TRAP assay exhibits excellent sensitivity. Consequently, we observed a 10-fold increase in sensitivity for cancer cells diluted 1000-fold with somatic cells. It thus appears that the use of AuNP-modified primers significantly improves the sensitivity and specificity of the traditional TRAP assay and may be an effective method by which PCR can be performed directly in concentrated cell lysates. © 2010 American Chemical Society.


PubMed | Institute for Collaborative Biotechnologies
Type: | Journal: BMJ case reports | Year: 2011

Understanding the actions performed by other people is a key aspect of social interaction, including in clinical settings where patients are learning from therapists and caregivers. While lesions of the left cerebral hemisphere induce praxic disorders, the hemispheric specialisation of intention understanding remains unclear. Do patients with a right hemispheric lesion understand the intentions of other people properly? The present study investigates how a split-brain patient understands the means (what) and intentions (why) of the actions of other people. Results show a significant left hemispheric dominance for understanding what is done, and a significant right hemispheric dominance for understanding why an action is carried out. This discovery might have important clinical implications in neurological patients, especially when those with right hemisphere lesions are faced with important decisions related to the interpretation of others intentions.

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