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Wednesday, December 4th, 2019
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| 10:52a | Controlling attention with brain waves Having trouble paying attention? MIT neuroscientists may have a solution for you: Turn down your alpha brain waves. In a new study, the researchers found that people can enhance their attention by controlling their own alpha brain waves based on neurofeedback they receive as they perform a particular task. The study found that when subjects learned to suppress alpha waves in one hemisphere of their parietal cortex, they were able to pay better attention to objects that appeared on the opposite side of their visual field. This is the first time that this cause-and-effect relationship has been seen, and it suggests that it may be possible for people to learn to improve their attention through neurofeedback. “There’s a lot of interest in using neurofeedback to try to help people with various brain disorders and behavioral problems,” says Robert Desimone, director of MIT’s McGovern Institute for Brain Research. “It’s a completely noninvasive way of controlling and testing the role of different types of brain activity.” It’s unknown how long these effects might last and whether this kind of control could be achieved with other types of brain waves, such as beta waves, which are linked to Parkinson’s disease. The researchers are now planning additional studies of whether this type of neurofeedback training might help people suffering from attentional or other neurological disorders. Desimone is the senior author of the paper, which appears in Neuron on Dec. 4. McGovern Institute postdoc Yasaman Bagherzadeh is the lead author of the study. Daniel Baldauf, a former McGovern Institute research scientist, and Dimitrios Pantazis, a McGovern Institute principal research scientist, are also authors of the paper. Alpha and attention There are billions of neurons in the brain, and their combined electrical signals generate oscillations known as brain waves. Alpha waves, which oscillate in the frequency of 8 to 12 hertz, are believed to play a role in filtering out distracting sensory information. Previous studies have shown a strong correlation between attention and alpha brain waves, particularly in the parietal cortex. In humans and in animal studies, a decrease in alpha waves has been linked to enhanced attention. However, it was unclear if alpha waves control attention or are just a byproduct of some other process that governs attention, Desimone says. To test whether alpha waves actually regulate attention, the researchers designed an experiment in which people were given real-time feedback on their alpha waves as they performed a task. Subjects were asked to look at a grating pattern in the center of a screen, and told to use mental effort to increase the contrast of the pattern as they looked at it, making it more visible. During the task, subjects were scanned using magnetoencephalography (MEG), which reveals brain activity with millisecond precision. The researchers measured alpha levels in both the left and right hemispheres of the parietal cortex and calculated the degree of asymmetry between the two levels. As the asymmetry between the two hemispheres grew, the grating pattern became more visible, offering the participants real-time feedback. Although subjects were not told anything about what was happening, after about 20 trials (which took about 10 minutes), they were able to increase the contrast of the pattern. The MEG results indicated they had done so by controlling the asymmetry of their alpha waves. “After the experiment, the subjects said they knew that they were controlling the contrast, but they didn’t know how they did it,” Bagherzadeh says. “We think the basis is conditional learning — whenever you do a behavior and you receive a reward, you’re reinforcing that behavior. People usually don’t have any feedback on their brain activity, but when we provide it to them and reward them, they learn by practicing.”
Although the subjects were not consciously aware of how they were manipulating their brain waves, they were able to do it, and this success translated into enhanced attention on the opposite side of the visual field. As the subjects looked at the pattern in the center of the screen, the researchers flashed dots of light on either side of the screen. The participants had been told to ignore these flashes, but the researchers measured how their visual cortex responded to them. One group of participants was trained to suppress alpha waves in the left side of the brain, while the other was trained to suppress the right side. In those who had reduced alpha on the left side, their visual cortex showed a larger response to flashes of light on the right side of the screen, while those with reduced alpha on the right side responded more to flashes seen on the left side. “Alpha manipulation really was controlling people’s attention, even though they didn’t have any clear understanding of how they were doing it,” Desimone says. Persistent effect After the neurofeedback training session ended, the researchers asked subjects to perform two additional tasks that involve attention, and found that the enhanced attention persisted. In one experiment, subjects were asked to watch for a grating pattern, similar to what they had seen during the neurofeedback task, to appear. In some of the trials, they were told in advance to pay attention to one side of the visual field, but in others, they were not given any direction. When the subjects were told to pay attention to one side, that instruction was the dominant factor in where they looked. But if they were not given any cue in advance, they tended to pay more attention to the side that had been favored during their neurofeedback training. In another task, participants were asked to look at an image such as a natural outdoor scene, urban scene, or computer-generated fractal shape. By tracking subjects’ eye movements, the researchers found that people spent more time looking at the side that their alpha waves had trained them to pay attention to. “It is promising that the effects did seem to persist afterwards,” says Desimone, though more study is needed to determine how long these effects might last. The research was funded by the McGovern Institute. |
| 1:00p | Investigating the rise of oxygenic photosynthesis About 2.4 billion years ago, at the end of the Archean Eon, a planet-wide increase in oxygen levels called the Great Oxidation Event (GOE) created the familiar atmosphere we all breathe today. Researchers focused on life's origins widely agree that this transition event was caused by the global proliferation of photosynthetic microbes capable of splitting water to make molecular oxygen (O2). However, according to Tanja Bosak, associate professor in MIT’s Department of Earth, Atmospheric, and Planetary Sciences (EAPS), researchers don’t know how long before the GOE these organisms evolved. Bosak’s new research, published today in Nature, suggests it might now be even harder to pin down the emergence of oxygen-producing microbes in the geologic record. A signal in the rocks The first microbes to make oxygen did not leave a diary behind, so scientists must search for subtle clues of their emergence that could have survived the intervening few billion years. Complicating things further, while evidence of the GOE is found all over the Earth, these early colonies of oxygen-producing organisms would likely have first existed in small ponds or bodies of water. Any record of them would be geographically isolated. Some scientists consider localized evidence of the mineral manganese oxide in ancient sediments to be an indicator (or proxy) for the existence of oxygen-producing organisms. This is because manganese oxidation was only thought to be possible in the presence of significant amounts of O2, more than normally existed in the atmosphere pre-GOE. Thus, finding evidence of manganese oxide in sediments predating the GOE would suggest oxygen-producing organisms had evolved by that time and were active in the area. But it turns out there’s more than one way to oxidize manganese. Anaerobic microbes change the game As described in the new paper, Bosak and her former postdoc, Mirna Daye, discovered that colonies of modern microbes can perform this process in anaerobic environments typical of the late Archean Eon. Unlike the organisms that caused the GOE, Daye and Bosak’s microbes use sulfide, instead of water, to perform photosynthesis, so they do not create molecular oxygen as a byproduct. Most scientists think that this type of anaerobic photosynthesis emerged as a precursor system to the more familiar oxygenic photosynthesis that ushered in the GOE, and Daye and Bosak’s microbes contain genetic machinery similar to what is thought to have existed before the evolution of bacteria capable of making oxygen. The Bosak group’s demonstration of manganese oxidation in an anaerobic environment means that evidence of ancient manganese oxide may not be a reliable proxy for the local evolution of oxygen-producing life. It could just be a signal for the presence of other organisms already thought to be widespread at that time. Bosak’s co-authors include associate professor of geobiology Gregory Fournier, along with former postdocs Mirna Daye and Mihkel Pajusalu of MIT’s EAPS department; Vanja Klepac-Ceraj, Sophie Rowland, and Anna Farrell-Sherman of Wellesley College; Nicolas Beukes of the University of Johannesburg; and Nobumichi Tamura of Berkley National Laboratory. Questioning ancient manganese “Discovering new mechanisms by which manganese oxide might be created in the Archean environments, before the rise of oxygen, is tremendously interesting because many of the proxies that we have [used] for the presence of oxygen [and therefore, microbes capable of producing it] in the environment in the first half of Earth’s history are … actually proxies for the presence of manganese oxide,” says Ariel Anbar, professor at the Arizona State University School of Earth and Space Exploration, who was not involved in the research. “That forces us to think more deeply about the proxies that we're using and whether they really are indicative of O2 or not.” The study of the ancient Earth has always been challenging, as evidence gets recycled by geological processes and otherwise lost to the wear and tear of time. Researchers have only fragmented and inferred data that they can use to develop theories. “What we are finding is not necessarily saying that these people who are interpreting these blips of oxygen before the GOE [are] wrong. It just gives me huge pause,” says Bosak, “The fact that we threw in some microbes and found these processes that were just never considered tells us that we really don't understand a lot about how life and the environment coevolved.” |
| 1:59p | Monthly birth control pill could replace daily doses Oral contraceptives are one of the most popular forms of birth control: In the United States, about 12 percent of women between 15 and 49 use them. However, their effectiveness depends on being taken every day, and it is estimated that about 9 percent of women taking birth control pills become pregnant each year. MIT researchers are now developing an oral contraceptive that only has to be taken once a month, which could reduce unintended pregnancies that result from forgetting to take a daily dose. This kind of monthly contraceptive could have a significant impact on the health of women and their families, especially in the developing world, the researchers say. “We are hopeful that this work — the first example ever of a month-long pill or capsule to our knowledge — will someday lead to potentially new modalities and options for women’s health as well as other indications,” says Robert Langer, the David H. Koch Institute Professor at MIT. The new contraceptive is contained within a gelatin-coated capsule and can carry three weeks’ worth of a contraceptive drug. This capsule remains in the stomach after being swallowed and gradually releases the drug. Tests in pigs showed that this kind of drug release can achieve the same concentration of the drug in the bloodstream as taking a daily dose. Langer and Giovanni Traverso, an assistant professor of mechanical engineering at MIT and a gastroenterologist at Brigham and Women’s Hospital, are the senior authors of the study, which appears today in Science Translational Medicine. Ameya Kirtane, a senior postdoc at MIT’s Koch Institute for Integrative Cancer Research, and Tiffany Hua, a former technical associate at MIT, are the lead authors of the paper. Long-term delivery The new contraceptive pill is based on star-shaped drug delivery systems that the MIT team previously developed, which can remain in the digestive tract for days or weeks after being swallowed. The delivery systems are placed in gelatin capsules that dissolve once they reach the stomach, allowing the folded arms of the star to expand and slowly release their payload. In their earlier studies, the researchers loaded the capsules with drugs to treat malaria, as well as HIV drugs, which currently have to be taken every day. Much of this work has been funded by the Bill and Melinda Gates Foundation, which urged the team to adapt the capsule to deliver long-lasting contraceptive drugs. Previous research has suggested that people are better at remembering to take medicine when they have to take it only weekly or monthly, instead of daily. To make their new contraceptive pill last for three to four weeks, the researchers had to incorporate stronger materials than those used in the earlier versions, which could survive in the harsh environment of the stomach for up to two weeks. The researchers tested materials by soaking them in simulated gastric fluid, which is very acidic, and found that two types of polyurethane worked best for the arms and the central core of the star. The researchers loaded the contraceptive drug levonorgestrel into the arms of the device and found that by changing the concentrations of the polymers that they mix with the drug, they can control the rate at which it is released. Once the capsule reaches the stomach it expands and becomes lodged in place. In a study of pigs, the researchers found that the capsules could release the drug at a fairly constant rate for up to four weeks. The concentration of the drug found in the pigs’ bloodstream was similar to the amount that would be present after ingesting daily levonorgestrel tablets. However, the capsules maintained these drug levels for nearly a month, while the tablets last for only a day. For use in humans, the capsule would be designed to break down after three or four weeks and exit the body through the digestive tract. The researchers are working on several possible ways to trigger the arms to break off, including through changes in pH, changes in temperature, or exposure to certain chemicals. “Lack of access to contraceptives is a global health issue that contributes to unnecessary maternal and newborn deaths every year,” says Kimberly Scarsi, an associate professor of pharmacy practice and science at the University of Nebraska Medical Center, who was not involved in the research. “A once-monthly oral contraceptive would provide a discreet, noninvasive birth control option that could significantly improve medication adherence to give women more control over their health and family planning decisions.” Health impact Lyndra Therapeutics, a company founded by Langer, Traverso, and others, recently received a $13 million grant from the Gates Foundation to further develop the monthly contraceptive pill so that it can be tested in humans. “Through the development of these technologies, we aim to transform people’s experience with taking medications by making it easier, with more infrequent dosing in the first once-a-month, orally delivered drug system. We’re very committed to getting these technologies to people over the coming years,” says Traverso, who said he anticipates human tests may be possible within three to five years. Improved contraception not only has health benefits, but also makes it easier for women to go to school and financially support themselves and their families. However, according to the World Health Organization, 214 million women of reproductive age in developing countries who want to avoid pregnancy are not using a modern contraceptive method, such as birth control pills. “Coming up with a monthly version of a contraceptive drug could have a tremendous impact on global health,” Kirtane says. “The impact that oral contraceptives can have on human health and gender equality cannot be overstated.” The researchers also believe that such a pill could be appealing for women who would prefer a long-lasting oral contraceptive over other long-term contraceptives such as intrauterine devices. “Even with all these long-acting devices available, there’s a certain population who prefers to take medications orally rather than have something implanted,” Kirtane says. “For those patients, something like this would be extremely helpful.” The research was funded by the Bill and Melinda Gates Foundation. Other MIT authors of the study are Alison Hayward, Aniket Wahane, Aaron Lopes, Taylor Bensel, Sierra Brooks, Declan Gwynne, Jacob Wainer, Joy Collins, and Siid Tamang. Ambika Bajpayee of Northeastern University and Frank Stanczyk and Lihong Ma of the University of Southern California are also authors of the paper. |
| 5:00p | How biomarkers can record and reconstruct climate trends Nestled within sediments that accumulate in marine environments, a certain class of molecule-sized fossils (biomarkers) sneakily record surface-water temperature changes over time. For almost two decades, scientists have used these molecules, found in cell membranes of organisms and called glycerol dibiphytanyl glycerol tetraether lipids (GDGTs), to reconstruct climate trends experienced over both regional and local marine environments. These microorganisms optimize cell membrane fluidity by adjusting the chemical composition and number of cell membrane lipids collectively known as TEX86 in response to environmental temperature changes fairly reliably: Relatively more lipids with a greater number of carbon rings are thought to be produced at higher temperatures. But a mystery remained: No one fully underderstood the mechanisms by which the complex membrane-spanning GDGTs encoded information about temperature, or which organisms actually contributed to the sedimentary GDGT signals. That's now set to change, thanks to scientists associated with the MIT Department of Earth, Atmospheric and Planetary Sciences (EAPS). Former EAPS postdoc Paula Welander, now an associate professor of earth systems science at Stanford University, recently led an effort to understand just how GDGTs are built, as well as how that information relates to the GDGTs produced in the oceans today and, potentially, in the distant past. In a study published last month in PNAS, Welander — along with first-author Zhirui Zeng of Stanford University and colleagues from Stanford and MIT — employed a combined organic geochemical, bioinformatic, and microbiological approach to fill in the details on GDGT biosynthesis. To start, the researchers identified a related type of archaeon, called Sulfolobus acidocaldarius, that produced GDGTs with carbon rings, much like the GDGTs produced by marine organisms. While S. acidocaldarius does not grow in marine environments, a genetically tractable archaeal system is already in place for this model organism — that is, scientists can genetically manipulate it by inserting or deleting genes and seeing how those changes affect its physiology and its membrane lipids. S. acidocaldarius is also well-characterized, and also grows quickly, enabling researchers to study their manipulations within days, rather than weeks or months. Within S. acidocaldarius, the researchers found three genes that might encode the ring-building mechanisms in GDGTs, and then they deleted them one by one. These mutants showed the scientists that only two of the deletions affected the resulting proteins, which influenced the number of rings present in the GDGTs. When they performed the two deletions together, the new GDGTs no longer contained rings. To further confirm the roles the two genes play in ring-building, the researchers expressed the genes in another organism that doesn’t normally produce GDGTs with rings, Methanosarcina acetivorans. Once the genes were expressed, M. acetivorans began to produce GDGTs containing carbon rings. To study the GDGTs produced, Welander, a microbiologist, turned to former EAPS postdoc Xiaolei Liu, now assistant professor of organic geochemistry at the University of Oklahoma, and Roger Summons, the Schlumberger Professor of Geobiology in EAPS. Liu, the world’s leading expert on identifying GDGTs by mass spectrometry, was not only able to confirm that two genes were needed to make the cyclized (ring) GDGT, but also that they operated in a sequential manner. One gene encodes a protein, which adds rings near the center of the molecule, and the second gene's produced protein adds more rings to the outer edges. Further, the researchers analyzed the phylogenetics to pinpoint the source of these cyclized GDGTs, which is a considerable source of uncertainty with respect to their use as paleotemperature proxies. “This was an exciting collaboration to participate in because earlier work conducted in our laboratory suggested that there may be multiple clades of archaea contributing to the TEX86 signal in the ocean,” Summons says. “The new research shows that this does not seem to be the case and that it is one clade, the marine Thaumarchaeota [not Euryarchaeota], that appears responsible, thereby improving the focus for future research directions.” This study was funded by the Simons Foundation Collaboration on the Origins of Life, the U.S. National Science Foundation, and the U.S. Department of Energy. |
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