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News Article | May 8, 2017
Site: www.eurekalert.org

CINCINNATI--Changes in female hormones may trigger headaches in adolescent girls, but their effect may depend on age and their stage of pubertal development, according to a new study from researchers at University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center. The study, "Ovarian Hormones, Age and Pubertal Development and their Association with Days of Headache Onset in Girls with Migraine: An Observational Cohort Study" is currently available in the online edition of Cephalalgia, the scholarly journal of the International Headache Society. The study found that higher levels of the sex hormone progesterone were associated with fewer headaches in older teenagers, while lower levels resulted in more headache in that group. In younger girls, the opposite appears to be true. "Ours is the first study to show that migraine headaches might also be influenced by female hormones in girls with migraine," says Vincent Martin, MD, professor in the UC Division of General Internal Medicine and co-director of the Headache and Facial Pain Center at the UC Gardner Neuroscience Institute. "While low and declining estrogen levels are thought to precipitate migraine in adult women we found that progesterone to be the most important trigger factor in these young girls. However, this effect seemed to differ depending on the age of the girls and their pubertal development." Nationally, about 10 percent of school age children suffer from migraine, according to the Migraine Research Foundation (MRF). As adolescence approaches, the incidence of migraine increases rapidly in girls and by age 17 about 8 percent of boys and 23 percent of girls have experienced migraine, the MRF reports. Past studies have shown that female hormones are an important contributor for migraine in adult women, explains Martin, also a UC Health physician. Two thirds of adult women will develop migraine attacks of that occur shortly before or during menstrual bleeding. These attacks have been called "menstrual migraine." Low and declining levels of estrogen are thought to trigger attacks of menstrual migraine. Prior to this study the contribution of female hormones on migraine was unknown in girls and at what age this might occur, says Martin. "There is a dramatic change in the way that female hormones affect migraine that occurs during puberty," says Martin. "Prior to puberty progesterone has little effect on migraine, but after puberty high progesterone levels are associated with fewer headaches and low progesterone levels have more headache." Researchers as part of a 13-month study examined 34 girls experiencing migraine distributed across three age strata, ages 8 to 11, 12 to 15 and 16 to 17. Daily urine samples were collected and the occurrence and severity of headaches was recorded in diary for a 90-day period. The urine samples were evaluated for metabolites of the sex hormones estrogen and progesterone to determine if their presence was associated with days of headache onset or severity. All participants were patients of Cincinnati Children's Headache Center. The adolescents were offered a nominal stipend to encourage study compliance. Higher levels of progesterone appeared to be associated with reduced frequency of headaches in older teens. In the 16 to 17 age group there was a 42 percent chance of having a headache when levels of progesterone were low in urine samples, while when levels of the hormone was higher the chance of headache dropped to 24 percent, says Martin. In the 8 to 11 age group, there was 15 percent chance of suffering from migraine or headache when levels of progesterone were low, but a 20 percent chance of migraine or headache when high levels of progesterone were found in the urine, explains Martin. "The shifting contribution of female hormones to migraine occurrence from pre-pubertal girls through puberty into adulthood suggests a very dynamic process," says Andrew Hershey, MD, PhD, endowed chair and director of neurology at Cincinnati Children's Hospital Medical Center. "As the brain is developing in these girls there may be differences in the brain receptors sensitivity and their roles in migraine occurrence. The role of these receptors appear to shift from progesterone to estrogen as these girls progress through puberty. As the brain matures it could respond differently to hormones than a non-maturated brain." Girls may first start entering puberty between age 8-10 years old, although their first period may not be until age 12 or later. As they progress through this pubertal development, there may be cyclic hormonal fluctuations and irregular menstrual periods, explains Hershey. "We have previously demonstrated that a monthly headache pattern can begin during these early stages. As they age, their menstrual periods become more regular as do hormone fluctuations and by age 17, most girls are demonstrating adult hormone patterns," says Hershey. "But just having fluctuations in hormones or regular menstrual periods isn't enough to account for the differences in headache severity and onset displayed by younger girls compared to older teens." Martin says the research team was able to account for cyclic changes of hormones and that they were not found to be predictive of headache onset. "What I can say with the urine progesterone levels is that they were preventive in the older teens and that was more of an adult response; it is what you would expect to see in older women." "Our study suggests that female hormones play an important role in triggering headaches in young girls and that their response to hormones seems to change at the time of puberty," says Martin. "Since migraine commonly begins during puberty in girls one might ask whether a change in response to hormones might represent the initiating factor for migraine in some girls- kind of like the "big bang" theory of migraine." Martin and Hershey teamed with Scott W. Powers, PhD, professor of pediatrics at UC and co-director of the Cincinnati Children's Headache Center; Marielle Kabbouche, MD, professor of pediatrics at UC and director of the Acute and Inpatient Headache Program at Cincinnati Children's; Hope O'Brien, MD, associate professor of pediatrics at UC and program director of Headache Medicine Education at Cincinnati Children's; and Joanne Kacperski, MD, assistant professor of pediatrics at UC and director of the Post Headache Concussion Program at Cincinnati Children's. Team members also included Cincinnati Children's researchers, Janelle Allen, Susan LeCates, Polly Vaughan and Shannon White and Timothy Houle, PhD, Harvard University. The study received financial support from the National Headache Foundation and the Driskill Foundation. Martin is president of the National Headache Foundation. He is a speaker for Teva Pharmaceutical Industries, Allergan Plc., Avanir Pharmaceuticals and Depomed, Inc. Martin is also a consultant for NeuroScion, Avanir Pharmaceuticals, Depomed, Inc., Eli Lilly and Company, Amgen Inc., and Alder Biopharmaceuticals. Hershey is a consultant for Allergan Plc., Amgen Inc., Curelator Headache, Depomed, Inc. and Eli Lilly and Company.


News Article | May 2, 2017
Site: www.eurekalert.org

The National Academy of Sciences announced today the election of 84 new members and 21 foreign associates in recognition of their distinguished and continuing achievements in original research. The National Academy of Sciences announced today the election of 84 new members and 21 foreign associates in recognition of their distinguished and continuing achievements in original research. Those elected today bring the total number of active members to 2,290 and the total number of foreign associates to 475. Foreign associates are nonvoting members of the Academy, with citizenship outside the United States. Newly elected members and their affiliations at the time of election are: Bates, Frank S.; Regents Professor, department of chemical engineering and materials science, University of Minnesota, Minneapolis Beilinson, Alexander; David and Mary Winton Green University Professor, department of mathematics, The University of Chicago, Chicago Bell, Stephen P.; investigator, Howard Hughes Medical Institute; and professor of biology, department of biology, Massachusetts Institute of Technology, Cambridge Bhatia, Sangeeta N.; John J. (1929) and Dorothy Wilson Professor, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge Buzsáki, György; professor, Neuroscience Institute, departments of physiology and neuroscience, New York University Langone Medical Center, New York City Carroll, Dana; distinguished professor, department of biochemistry, University of Utah School of Medicine, Salt Lake City Cohen, Judith G.; Kate Van Nuys Page Professor of Astronomy, department of astronomy, California Institute of Technology, Pasadena Crabtree, Robert H.; Conkey P. Whitehead Professor of Chemistry, department of chemistry, Yale University, New Haven, Conn. Cronan, John E.; professor and head of microbiology, professor of biochemistry, and Microbiology Alumni Professor, department of microbiology, University of Illinois, Urbana-Champaign Cummins, Christopher C.; Henry Dreyfus Professor of Chemistry, Massachusetts Institute of Technology, Cambridge Darensbourg, Marcetta Y.; distinguished professor of chemistry, department of chemistry, Texas A&M University, College Station DeVore, Ronald A.; The Walter E. Koss Professor and distinguished professor, department of mathematics, Texas A&M University, College Station Diamond, Douglas W.; Merton H. Miller Distinguished Service Professor of Finance, The University of Chicago, Chicago Doe, Chris Q.; investigator, Howard Hughes Medical Institute; and professor of biology, Institute of Molecular Biology, University of Oregon, Eugene Duflo, Esther; Co-founder and co-Director of the Abdul Latif Jameel Poverty Action Lab, and Professor of Poverty Alleviation and Development Economics, Massachusetts Institute of Technology, Cambridge Edwards, Robert Haas; professor of neurology and physiology, University of California, San Francisco Firestone, Mary K.; professor and associate dean of instruction and student affairs, department of environmental science policy and management, University of California, Berkeley Fischhoff, Baruch; Howard Heinz University Professor, department of social and decision sciences and department of engineering and public policy, Carnegie Mellon University, Pittsburgh Ginty, David D.; investigator, Howard Hughes Medical Institute; and Edward R. and Anne G. Lefler Professor of Neurobiology, department of neurobiology, Harvard Medical School, Boston Glass, Christopher K.; professor of cellular and molecular medicine and professor of medicine, University of California, San Diego Goldman, Yale E.; professor, department of physiology, Pennsylvania Muscle Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia González, Gabriela; spokesperson, LIGO Scientific Collaboration; and professor, department of physics and astronomy, Louisiana State University, Baton Rouge Hagan, John L.; John D. MacArthur Professor of Sociology and Law, department of sociology, Northwestern University, Evanston, Ill. Hatten, Mary E.; Frederick P. Rose Professor, laboratory of developmental neurobiology, The Rockefeller University, New York City Hebard, Arthur F.; distinguished professor of physics, department of physics, University of Florida, Gainesville Jensen, Klavs F.; Warren K. Lewis Professor of Chemical Engineering and professor of materials science and engineering, Massachusetts Institute of Technology, Cambridge Kahn, Barbara B.; vice chair for research strategy and George R. Minot Professor of Medicine at Harvard Medical School, Beth Israel Deaconess Medical Center, Boston Kinder, Donald R.; Philip E. Converse Collegiate Professor of Political Science and Psychology and research scientist, department of political science, Center for Political Studies, Institute for Social Research, University of Michigan, Ann Arbor Lazar, Mitchell A.; Willard and Rhoda Ware Professor in Diabetes and Metabolic Diseases, and director, Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania Perelman School of Medicine, Philadelphia Locksley, Richard M.; investigator, Howard Hughes Medical Institute; and professor, department of medicine (infectious diseases), and Marion and Herbert Sandler Distinguished Professorship in Asthma Research, University of California, San Francisco Lozano, Guillermina; professor and chair, department of genetics, The University of Texas M.D. Anderson Cancer Center, Houston Mavalvala, Nergis; Curtis and Kathleen Marble Professor of Astrophysics and associate head, department of physics, Massachusetts Institute of Technology, Cambridge Moore, Jeffrey Scott; Murchison-Mallory Professor of Chemistry, department of chemistry, University of Illinois, Urbana-Champaign Moore, Melissa J.; chief scientific officer, mRNA Research Platform, Moderna Therapeutics, Cambridge, Mass.; and Eleanor Eustis Farrington Chair of Cancer Research Professor, RNA Therapeutics Institute, University of Massachusetts Medical School, Worcester Nunnari, Jodi M.; professor, department of molecular and cellular biology, University of California, Davis O'Farrell, Patrick H.; professor of biochemistry and biophysics, department of biochemistry and biophysics, University of California, San Francisco Ort, Donald R.; research leader and Robert Emerson Professor, USDA/ARS Global Change and Photosynthesis Research Unit, departments of plant biology and crop sciences, University of Illinois, Urbana-Champaign Parker, Gary; professor, department of civil and environmental engineering and department of geology, University of Illinois, Urbana-Champaign Patapoutian, Ardem; investigator, Howard Hughes Medical Institute; and professor, department of molecular and cellular neuroscience, The Scripps Research Institute, La Jolla, Calif. Pellegrini, Claudio; distinguished professor emeritus, department of physics and astronomy, University of California, Los Angeles Pikaard, Craig, S.; investigator, Howard Hughes Medical Institute and Gordon and Betty Moore Foundation; and distinguished professor of biology and molecular and cellular biochemistry, department of biology, Indiana University, Bloomington Read, Nicholas; Henry Ford II Professor of Physics and professor of applied physics and mathematics, Yale University, New Haven, Conn. Roediger, Henry L.; James S. McDonnell Distinguished and University Professor of Psychology, department of psychology and brain sciences, Washington University, St. Louis Rosenzweig, Amy C.; Weinberg Family Distinguished Professor of Life Sciences, and professor, departments of molecular biosciences and of chemistry, Northwestern University, Evanston, Ill. Seto, Karen C.; professor, Yale School of Forestry and Environmental Studies, New Haven, Conn. Seyfarth, Robert M.; professor of psychology and member of the graduate groups in anthropology and biology, University of Pennsylvania, Philadelphia Sibley, L. David; Alan A. and Edith L. Wolff Distinguished Professor in Molecular Microbiology, department of molecular microbiology, Washington University School of Medicine, St. Louis Spielman, Daniel A.; Henry Ford II Professor of Computer Science and Mathematics, departments of computer science and mathematics, Yale University, New Haven, Conn. Sudan, Madhu; Gordon McKay Professor of Computer Science, John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, Mass. Tishkoff, Sarah; David and Lyn Silfen University Professor, departments of genetics and biology, University of Pennsylvania, Philadelphia Van Essen, David C.; Alumni Professor of Neurobiology, department of anatomy and neurobiology, Washington University School of Medicine, St. Louis Vidale, John E.; professor, department of earth and space sciences, University of Washington, Seattle Wennberg, Paul O.; R. Stanton Avery Professor of Atmospheric Chemistry and Environmental Science and Engineering, California Institute of Technology, Pasadena Wilson, Rachel I.; Martin Family Professor of Basic Research in the Field of Neurobiology, department of neurobiology, Harvard Medical School, Boston Zachos, James C.; professor, department of earth and planetary sciences, University of California, Santa Cruz, Santa Cruz Newly elected foreign associates, their affiliations at the time of election, and their country of citizenship are: Addadi, Lia; professor and Dorothy and Patrick E. Gorman Chair of Biological Ultrastructure, department of structural science, Weizmann Institute of Science, Rehovot, Israel (Israel/Italy) Folke, Carl; director and professor, The Beijer Institute of Ecological Economics, Royal Swedish Academy of Sciences, Stockholm, Sweden (Sweden) Freeman, Kenneth C.; Duffield Professor of Astronomy, Mount Stromlo and Siding Spring Observatories, Research School of Astronomy and Astrophysics, Australian National University, Weston Creek (Australia) Lee, Sang Yup; distinguished professor, dean, and director, department of chemical and biomolecular engineering, Korea Advanced Institute of Science and Technology, Daejeon, South Korea (South Korea) Levitzki, Alexander; professor of biochemistry, unit of cellular signaling, department of biological chemistry, The Hebrew University of Jerusalem, Jerusalem (Israel) Peiris, Joseph Sriyal Malik; Tam Wah-Ching Professorship in Medical Science, School of Public Health, The University of Hong Kong, Pokfulam, Hong Kong, People's Republic of China (Sri Lanka) Robinson, Carol Vivien; Dr. Lee's Professor of Chemistry, Physical and Theoretical Chemistry Laboratory, University of Oxford, Oxford, England (United Kingdom) Thesleff, Irma; academician of science, professor, and research director, developmental biology program, Institute of Biotechnology, University of Helsinki, Helsinki (Finland) Underdal, Arild; professor of political science, department of political science, University of Oslo, Oslo, Norway (Norway) The National Academy of Sciences is a private, nonprofit institution that was established under a congressional charter signed by President Abraham Lincoln in 1863. It recognizes achievement in science by election to membership, and -- with the National Academy of Engineering and the National Academy of Medicine -- provides science, engineering, and health policy advice to the federal government and other organizations.


News Article | May 3, 2017
Site: www.prnewswire.com

Using live mice and computer simulations of neural circuits, the study authors found that the "mediodorsal" thalamus strengthens connections within the PFC rather than strictly relay information to the cortex as previously thought. This strengthening informs decisions by enabling PFC circuits to "hold in mind" experience-based rules on what to pay attention to, say the authors. "Our study provides the clearest demonstration to date that the mediodorsal thalamus or MD may be the conductor of connectivity between circuits as the brain attends to previously learned rules and makes decisions in real time," says study senior investigator Michael Halassa, MD, PhD, an assistant professor at NYU Langone's Neuroscience Institute. "This new understanding also implicates the thalamus in cognitive deficits that come with diseases known to proceed from connection problems in the cortex, from attention deficits to the psychosis seen in schizophrenia to sleep problems," says Halassa. "Our results support the theory that cognition in general could be improved by adjusting thalamic function." In the current study, researchers examined how the MD and PFC interact as mice used experience-based rules to determine which sensory stimuli to pay attention to (flash of light versus sound) to gain access to a food reward. The researchers found that enhancing MD activity magnified the ability of mice to "think," driving down by more than 25 percent their error rate in deciding which conflicting sensory stimuli to follow to find the reward. To the contrary, increasing the activity of prefrontal cortex directly destroyed the ability of the mice to make the right decision based on previous training (drove success down to a 50/50 chance in some cases). The interpretation is that this caused interconnected cortical circuits encoding conflicting rules to fire at the same time. The experiments suggest a new theory for how the mammalian brain operates, says Halassa.  It may have developed the flexibility to make complex decisions by wiring the many associations on which decisions depend into weakly connected cortical circuits. This strategy would only work though if the thalamus was there to amplify the connectivity (signaling strength) of just the circuits in the cortex appropriate for the current context. In terms of methods, Halassa and colleagues stitched into a certain spot in the DNA of nerve cells in these mice the code for a light-sensitive protein. With that in place, the team was able to turn on nerve cell signaling in the MD and PFC by shining light. At the same time, the team had implanted electrodes that measure patterns of nerve cell activity. The team then designed a test with steps that required mice to consider and combine sensory clues over time to find food as the team recorded brain circuit activity. Halassa says that these precise regimens have enabled his team to perform sophisticated behavioral tests in mice that were once done in non-human primates. Along with Halassa, the study was conducted by first author L. Ian Schmitt, Ralf Wimmer, Miho Nakajima, Sima Mofakham, and Michael Happ in the NYU Langone Neuroscience Institute. The study was funded supported by grants from the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the Brain and Behavior Research Foundation, the Sloan and Klingenstein foundations, and the Human Frontiers Science Program. To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/new-role-found-for-brain-region-focusing-attention-during-decision-making-300450823.html


News Article | May 3, 2017
Site: www.eurekalert.org

Long thought to simply pass on information received from the senses, the thalamus may also quickly assemble the circuits that enable successful decisions. This newfound function for this small, center-brain region is the main finding of a study led by researchers from NYU Langone Medical Center and published May 3 in the journal Nature. The study focuses on the part of the thalamus associated with the prefrontal cortex or PFC, the brain region traditionally linked to "executive functions" like working memory, the ability to focus attention, and decision-making. Using live mice and computer simulations of neural circuits, the study authors found that the "mediodorsal" thalamus strengthens connections within the PFC rather than strictly relay information to the cortex as previously thought. This strengthening informs decisions by enabling PFC circuits to "hold in mind" experience-based rules on what to pay attention to, say the authors. "Our study provides the clearest demonstration to date that the mediodorsal thalamus or MD may be the conductor of connectivity between circuits as the brain attends to previously learned rules and makes decisions in real time," says study senior investigator Michael Halassa, MD, PhD, an assistant professor at NYU Langone's Neuroscience Institute. "This new understanding also implicates the thalamus in cognitive deficits that come with diseases known to proceed from connection problems in the cortex, from attention deficits to the psychosis seen in schizophrenia to sleep problems," says Halassa. "Our results support the theory that cognition in general could be improved by adjusting thalamic function." In the current study, researchers examined how the MD and PFC interact as mice used experience-based rules to determine which sensory stimuli to pay attention to (flash of light versus sound) to gain access to a food reward. The researchers found that enhancing MD activity magnified the ability of mice to "think," driving down by more than 25 percent their error rate in deciding which conflicting sensory stimuli to follow to find the reward. To the contrary, increasing the activity of prefrontal cortex directly destroyed the ability of the mice to make the right decision based on previous training (drove success down to a 50/50 chance in some cases). The interpretation is that this caused interconnected cortical circuits encoding conflicting rules to fire at the same time. The experiments suggest a new theory for how the mammalian brain operates, says Halassa. It may have developed the flexibility to make complex decisions by wiring the many associations on which decisions depend into weakly connected cortical circuits. This strategy would only work though if the thalamus was there to amplify the connectivity (signaling strength) of just the circuits in the cortex appropriate for the current context. In terms of methods, Halassa and colleagues stitched into a certain spot in the DNA of nerve cells in these mice the code for a light-sensitive protein. With that in place, the team was able to turn on nerve cell signaling in the MD and PFC by shining light. At the same time, the team had implanted electrodes that measure patterns of nerve cell activity. The team then designed a test with steps that required mice to consider and combine sensory clues over time to find food as the team recorded brain circuit activity. Halassa says that these precise regimens have enabled his team to perform sophisticated behavioral tests in mice that were once done in non-human primates. Along with Halassa, the study was conducted by first author L. Ian Schmitt, Ralf Wimmer, Miho Nakajima, Sima Mofakham, and Michael Happ in the NYU Langone Neuroscience Institute. The study was funded supported by grants from the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the Brain and Behavior Research Foundation, the Sloan and Klingenstein foundations, and the Human Frontiers Science Program.

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