Researchers at the RIKEN Center for Biosystems Dynamics Research in Japan have developed a new system for keeping tissue viable for long-term study once transferred from an animal to a culture medium. The new system uses a microfluidic device made of polydimethylsiloxane (PDMS) with a porous membrane that can keep tissue from both drying out and from drowning in fluid. This study was published in the journal Analytical Sciences.
The team tested the device using tissue from the mouse suprachiasmatic nucleus, a complex part of the brain that governs circadian rhythms. By measuring the level of bioluminescence coming from the brain tissue, they were able to see that tissue kept alive by their system stayed active and functional for over 25 days with nice circadian activity. In contrast, neural activity in tissue kept in a conventional culture decreased by 6% after only 10 hours.
This new method will be useful in observing development and testing how tissues respond to drugs. Experiments with tissues are much more complex and provide important information such as cell to cell interaction, unlike seeded cells where such observation is difficult.
Research by University of Houston scientists discovered a possible link between nuclear receptor protein LXRβ (Liver X receptor Beta) and autism spectrum disorder. They found that nuclear receptor LXRβ deletion causes poor development of dentate gyrus, a part of brain’s hippocampus. The dentate gyrus, or DG, is responsible for emotion and memory and is known to be involved in autism spectrum disorders (ASD).
This study is led by Margaret Warner and Jan-Åke Gustafsson. The results are published in journal Proceedings of the National Academy of Sciences.”Our findings suggest early changes in dentate gyrus neurogenesis ultimately provide an aberrant template upon which to build the circuitry that is involved in normal social function,” said Warner.
Researchers conducted an animal study using LXRβ-deficient mice. Behavior analysis of these mice showed autistic-like behaviors, including social interaction deficits and repetitive behavior.”Knocking out LXRβ led to autistic behavior and reduced cognitive flexibility,” said Warner. “In this paper, we share our findings that that deletion of the LXRβ (Liver X receptor Beta) causes hypoplasia or underdevelopment in the dentate gyrus and autistic-like behaviors, including abnormal social interaction and repetitive behavior.”
Citation: Cai, Yulong, Xiaotong Tang, Xi Chen, Xin Li, Ying Wang, Xiaohang Bao, Lian Wang, Dayu Sun, Jinghui Zhao, Yan Xing, Margaret Warner, Haiwei Xu, Jan-Åke Gustafsson, and Xiaotang Fan. “Liver X receptor β regulates the development of the dentate gyrus and autistic-like behavior in the mouse.” Proceedings of the National Academy of Sciences, 2018, 201800184. doi:10.1073/pnas.1800184115.
The human brain is a complex network composed of approximately 100 billion neurons. With current computing power, it is impossible to simulate 100 percent working brain. Currently, researchers use simulating software called NEST to simulate the brain. NEST, a free, open-source simulation code in widespread use by the neuroscientific community and a core simulator of the European Human Brain Project.
“Since 2014, our software can simulate about one percent of the neurons in the human brain with all their connections,” says Markus Diesmann, Director at the Jülich Institute of Neuroscience and Medicine (INM-6). To achieve this impressive feat, the software requires the entire main memory of petascale supercomputers.
With NEST, the behavior of each neuron in the network is represented by a handful of mathematical equations. Future exascale computers, such as the post-K computer planned in Kobe and JUWELS in Jülich, will exceed the performance of today’s high-end supercomputers by 10- to 100-fold. For the first time, researchers will have the computer power available to simulate neuronal networks on the scale of the human brain.
While current simulation technology enabled researchers to begin studying large neuronal networks, it also represented a dead end on the way to exascale technology. Supercomputers are composed of about 100,000 small computers, called nodes, each equipped with many processors doing the actual calculations.
“Before a neuronal network simulation can take place, neurons and their connections need to be created virtually, which means that they need to be instantiated in the memory of the nodes. During the simulation, a neuron does not know on which of the nodes it has target neurons. Therefore, its short electric pulses need to be sent to all nodes. Each node then checks which of all these electric pulses are relevant for the virtual neurons that exist on this node,” explains Susanne Kunkel of KTH Royal Institute of Technology in Stockholm.
The current algorithm for network creation is efficient because all nodes construct their particular part of the network at the same time. However, sending all electric pulses to all nodes is not suitable for simulations on exascale systems.
“Checking the relevance of each electric pulse efficiently requires one Bit of information per processor for every neuron in the whole network. For a network of 1 billion neurons, a large part of the memory in each node is consumed by just this single Bit of information per neuron,” adds Markus Diesmann.
This is the main problem when simulating even larger networks: the amount of computer memory required per processor for the extra Bits per neuron increases with the size of the neuronal network. At the scale of the human brain, this would require the memory available to each processor to be 100 times larger than in today’s supercomputers. This, however, is unlikely to be the case in the next generation of supercomputers. The number of processors per compute node will increase, but the memory per processor and the number of compute nodes will rather stay the same.
The breakthrough published in Frontiers in Neuroinformatics is a new way of constructing the neuronal network in the supercomputer. Due to the algorithms, the memory required on each node no longer increases with network size. At the beginning of the simulation, the new technology allows the nodes to exchange information about who needs to send neuronal activity data to whom. Once this knowledge is available, the exchange of neuronal activity data between nodes can be organized such that a node only receives the information it requires. An additional Bit for each neuron in the network is no longer necessary.
While testing their new ideas, the scientists made an additional key insight, reports Susanne Kunkel: “When analyzing the new algorithms we realized that our novel technology would not only enable simulations on exascale systems, but it would also make simulations faster on presently available supercomputers.”
In fact, as the memory consumption is now under control, the speed of simulations becomes the main focus of further technological developments. For example, a large simulation of 0.52 billion neurons connected by 5.8 trillion synapses running on the supercomputer JUQUEEN in Jülich previously required 28.5 minutes to compute one second of biological time. With the improved data structures simulation, the time is reduced to 5.2 minutes.
“With the new technology we can exploit the increased parallelism of modern microprocessors a lot better than previously, which will become even more important in exascale computers,” remarks Jakob Jordan, lead author of the study, from Forschungszentrum Jülich.
“The combination of exascale hardware and appropriate software brings investigations of fundamental aspects of brain function, like plasticity and learning unfolding over minutes of biological time within our reach,” adds Markus Diesmann.
With one of the next releases of the simulation software NEST, the researchers will make their achievement freely available to the community as open source.
“We have been using NEST for simulating the complex dynamics of the basal ganglia circuits in health and Parkinson’s disease on the K computer. We are excited to hear the news about the new generation of NEST, which will allow us to run whole-brain-scale simulations on the post-K computer to clarify the neural mechanisms of motor control and mental functions,” says Kenji Doya of Okinawa Institute of Science and Technology (OIST).
“The study is a wonderful example of the international collaboration in the endeavor to construct exascale computers. It is important that we have applications ready that can use these precious machines from the first day they are available,” concludes Mitsuhisa Sato of the RIKEN Advanced Institute for Computer Science in Kobe.
Citation: Jordan, Jakob, Tammo Ippen, Moritz Helias, Itaru Kitayama, Mitsuhisa Sato, Jun Igarashi, Markus Diesmann, and Susanne Kunkel. “Extremely Scalable Spiking Neuronal Network Simulation Code: From Laptops to Exascale Computers.” Frontiers in Neuroinformatics 12 (2018). doi:10.3389/fninf.2018.00002.
Research funding: Helmholtz Portfolio Supercomputing and Modeling for the Human Brain (SMHB), Helmholtz young investigator group, EU 7th Framework Programme (Human Brain Project), EU Horizon 2020 research and innovation programme (Human Brain Project).
This image shows a sheet of glassy carbon electrodes patterned inside chips. Credit: Sam Kassegne, San Diego State University.
When people suffer spinal cord injuries and lose mobility in their limbs, the brain can still send clear electrical impulses and the limbs can still receive them, but the signal gets lost in the damaged spinal cord. The brain chip the researchers works by bypassing the damage and restoring movement.
The technology, known as a brain-computer interface, records and transmits signals through electrodes, which are tiny pieces of material that read signals from brain chemicals known as neurotransmitters. The device works by recording and analyzing brain signals and convert them into a relevant electrical signal pattern, these signals are then transmitted to the limb’s nerves, or even to a prosthetic limb, restoring mobility and motor function.
The current state-of-the-art material for electrodes in these devices is thin-film platinum. The problem is that these electrodes can fracture and fall apart over time, said one of the study’s lead investigators, Sam Kassegne, deputy director for the CSNE at SDSU and a professor in the mechanical engineering department. To overcome this problem researchers developed electrodes made out of glassy carbon, a form of carbon. This material is about 10 times smoother than granular thin-film platinum, meaning it corrodes less easily under electrical stimulation and lasts much longer than platinum or other metal electrodes. Researchers are using these new and improved brain-computer interfaces to record neural signals both along the brain’s cortical surface and from inside the brain at the same time.
A doctoral graduate student in Kassegne’s lab, Mieko Hirabayashi, is exploring a slightly different application of this technology. She’s working with rats to find out whether precisely calibrated electrical stimulation using these electrodes can cause new neural growth within the spinal cord with hope to replicate these results in humans. The new glassy carbon electrodes will allow her to stimulate, read the electrical signals of and detect the presence of neurotransmitters in the spinal cord better than ever before.
Citation: Vomero, Maria, Elisa Castagnola, Francesca Ciarpella, Emma Maggiolini, Noah Goshi, Elena Zucchini, Stefano Carli, Luciano Fadiga, Sam Kassegne, and Davide Ricci. “Highly Stable Glassy Carbon Interfaces for Long-Term Neural Stimulation and Low-Noise Recording of Brain Activity.” Scientific Reports 7 (2017): 40332. DOI:10.1038/srep40332. Research funding: National Science Foundation. Adapted from press release by San Diego State University.
Humans and other vertebrates depend on a portion of the brain called the hippocampus for learning, memory and their sense of location. Nerve cell structures in the adult hippocampus are sustained by factors whose identities have remained largely mysterious so far.
Now, research led by a Johns Hopkins University biologist Dr. Kuruvilla sheds light on the subject, potentially pointing the way to a better understanding of how the structure of nerve cells in the adult hippocampus may deteriorate, which can lead to Alzheimer’s disease and other neurological disorders.
In a paper in the journal Proceedings of the National Academy of Sciences, Kuruvilla and eight other scientists from two research institutions report that a protein that has primarily been studied for its role in early animal development also plays a surprising role in maintaining the structure of hippocampal neurons in adult mice.
The team studied a protein called Wnt5a, which belongs to a family of proteins that have been studied primarily for their functions during embryonic development and in nurturing neurons as the young brain forms. Using mice genetically altered to remove Wnt5a from the hippocampus, the team showed that the protein’s absence did not affect hippocampus development in young mice, but instead resulted in striking degradation of specific nerve cell structures called dendrites, which resemble clusters of tree branches, in adult mice. These findings suggest that the protein plays an important role in maintaining dendrite structures as the mouse ages.
The team went further by showing that when the Wnt5a protein was reintroduced after the dendrites had started to deteriorate in aged mice, the nerve cell structures were restored – to a degree the scientists did not expect.
The team also tested the ability of mice lacking Wnt5a in the hippocampus to perform learning and memory tasks. Behavior tests were run in a Morris Water Maze designed to show how well mice use spatial cues to navigate in a water pool and how long it takes them to learn to use a hidden platform to escape. They found that mutant mice – those without Wnt5a – were poor learners and had attenuated memory; their performance in behavioral tasks became progressively worse with age.
“Together, the findings from the Morris Water Maze test support an essential role for Wnt5a in the acquisition of spatial learning and memory storage in adult animals,” the authors wrote. In the brain, the hippocampus is the seat of short- and long-term memory and governs spatial orientation. Studies have shown that the brains of people with Alzheimer’s disease have structural alterations in dendrites, particularly in the hippocampus.
Kuruvilla said the experiments suggest avenues for further research on what may cause shrinkage of dendrites during neurological disorders. She emphasized, however, that it is premature to extrapolate these results in mice to humans.
While Kuruvilla was careful not to overstate the significance of the findings or how they may apply to cognitive disorders in humans, she said the results at least bring attention to the significance of studying molecular signals that maintain neurons in the adult brain. Compared to the wealth of information on signals that help in formation of neuronal connections in the developing brain, we know far less of how brain structure is sustained in adult life, she said.
Citation: Chih-Ming Chena, Lauren L. Oreficeb, Shu-Ling Chiuc, Tara A. LeGatesa, Samer Hattara, Richard L. Huganirc, Haiqing Zhaoa, Baoji Xub, and Rejji Kuruvillaa. “Wnt5a is essential for hippocampal dendritic maintenance and spatial learning and memory in adult mice.” PNAS 2017. DOI: 10.1073/pnas.1615792114 Research funding: National Institutes of Health. Adapted from press release by Johns Hopkins University.
Northwestern Medicine scientists showed for the first time that non-invasive brain stimulation can be used like a scalpel, rather than like a hammer, to cause a specific improvement in precise memory.
This is an individual receiving noninvasive brain stimulation (‘high-frequency, repetitive, transcranial electromagnetic stimulation’). Credit: Northwestern University
Precise memory, rather than general memory, is critical for knowing details such as the specific color, shape, and location of a building you are looking for, rather than simply knowing the part of town it’s in. This type of memory is crucial for normal functioning, and it is often lost in people with serious memory disorders.
“We show that it is possible to target the portion of the brain responsible for this type of memory and to improve it,” said lead author Joel Voss, assistant professor of medical social sciences at Northwestern University Feinberg School of Medicine. “People with brain injuries have problems with precise memory as do individuals with dementia, and so our findings could be useful in developing new treatments for these conditions.”
By stimulating the brain network responsible for spatial memory with powerful electromagnets, scientists improved the precision of people’s memory for identifying locations. This benefit lasted a full 24 hours after receiving stimulation and corresponded to changes in brain activity. “We improved people’s memory in a very specific and important way a full day after we stimulated their brains,” Voss said. The paper was published in Current Biology.
The research enhances scientific understanding of how memory can be improved using noninvasive stimulation. Most previous studies of noninvasive brain stimulation have found only very general and short-lived effects on thinking abilities, rather than highly specific and long-lasting effects on an ability such as precise memory.
The scientists used MRI to identify memory-related brain networks then stimulated them with noninvasive electromagnetic stimulation. Detailed memory tests were used to show that this improved spatial precision memory, and EEG was used to show that these memory improvements corresponded to indicators of improved brain network function.
Citation: Aneesha S. Nilakantan, Donna J. Bridge, Elise P. Gagnon, Stephen A. VanHaerents and Joel L. Voss. “Stimulation of the Posterior Cortical-Hippocampal Network Enhances Precision of Memory Recollection.” Current Biology 2017 pp: 310-318. DOI: 10.1016/j.cub.2016.12.042 Research funding: National Institute of Mental Health, National Institute on Aging National Institute of Neurological Disorders and Stroke and National Institutes of Health. Adapted from press release by Northwestern University.
Over millions of years, retroviruses have been incorporated into our human DNA, where they today make up almost 10 percent of the total genome. A research group at Lund University in Sweden has now discovered a mechanism through which these retroviruses may have an impact on gene expression. This means that they may have played a significant role in the development of the human brain as well as in various neurological diseases.
Retroviruses are a special group of viruses including some which are dangerous, such as HIV, while others are believed to be harmless. The viruses studied by Johan Jakobsson and his colleagues in Lund are called endogenous retroviruses (ERV) as they have existed in the human genome for millions of years. They can be found in a part of DNA that was previously considered unimportant, so-called junk-DNA a notion that researchers have now started to reconsider.
“The genes that control the production of various proteins in the body represent a smaller proportion of our DNA than endogenous retroviruses. They account for approximately 2 per cent, while retroviruses account for 8-10 per cent of the total genome. If it turns out that they are able to influence the production of proteins, this will provide us with a huge new source of information about the human brain”, says Johan Jakobsson.
And this is precisely what the researchers discovered. They have determined that several thousands of the retroviruses that have established themselves in our genome may serve as “docking platforms” for a protein called TRIM28. This protein has the ability to “switch off” not only viruses but also the standard genes adjacent to them in the DNA helix, allowing the presence of ERV to affect gene expression.
This switching-off mechanism may behave differently in different people since retroviruses are a type of genetic material that may end up in different places in the genome. This makes it a possible tool for evolution, and even a possible underlying cause of neurological diseases. In fact, there are studies that indicate a deviating regulation of ERV in several neurological diseases such as ALS, schizophrenia, and bipolar disorder.
The differences between mice and humans are particularly important in this context. Many of the retroviruses that have been built into the human DNA do not exist in species other than humans and our closest relatives gorillas and chimpanzees. They seem to have incorporated themselves into the genome some 35-45 million years ago when the evolutionary lineage of primates was divided between the Old and New World.
“Much of what we know about the overall development of the brain comes from the fruit fly, zebrafish, and mouse. However, if endogenous retroviruses affect brain function, and we have our own set of these ERV, the mechanisms they affect may have contributed to the development of the human brain”, says Johan Jakobsson.
Citation: Brattås, Per Ludvik, Marie E. Jönsson, Liana Fasching, Jenny Nelander Wahlestedt, Mansoureh Shahsavani, Ronny Falk, Anna Falk, Patric Jern, Malin Parmar, Johan Jakobsson. “TRIM28 Controls a Gene Regulatory Network Based on Endogenous Retroviruses in Human Neural Progenitor Cells.” Cell reports Volume 18, Issue 1, p1–11. DOI: 10.1016/j.celrep.2016.12.010 Adapted from press release by Lund University.
According to a new study by Université de Montréal’s School of Speech-Language Pathology and Audiology, part of UdeM’s medical faculty learning to play musical instrument help elderly to react faster and to stay alerted. The study is published in journal Brain and Cognition. The study shows that musicians have faster reaction times to sensory stimuli than non-musicians have.
According to lead researcher Simon Landry, this study has implications for preventing some effects of aging. “The more we know about the impact of music on really basic sensory processes, the more we can apply musical training to individuals who might have slower reaction times,” Landry said.
In his study, co-authored with his thesis advisor, audiology associate professor François Champoux, Landry compared the reaction times of 16 musicians and 19 non-musicians. Research subjects sat in a quiet, well-lit room with one hand on a computer mouse and the index finger of the other on a vibrotactile device, a small box that vibrated intermittently. They were told to click on the mouse when they heard a sound (a burst of white noise) from the speakers in front of them, or when the box vibrated, or when both happened.
Each of the three stimulations – audio, tactile and audio-tactile – was done 180 times. The subjects wore earplugs to mask any buzzing “audio clue” when the box vibrated. “We found significantly faster reaction times with musicians for auditory, tactile and audio-tactile stimulations,” Landry writes in his study.
“These results suggest for the first time that long-term musical training reduces simple non-musical auditory, tactile and multisensory reaction times.” The musicians were recruited from UdeM’s music faculty, started playing between ages 3 and 10, and had at least seven years of training. There were eight pianists, 3 violinists, two percussionists, one double bassist, one harpist and one viola player. All but one (a violinist) also mastered a second instrument or more. The non-musicians were students at the School of Speech-Language Pathology. As with the musicians, roughly half were undergraduates and half graduates.
Landry, whose research interest is in how sound and touch interact, said his study adds to previous ones that looked at how musicians’ brains process sensory illusions. “The idea is to better understand how playing a musical instrument affects the senses in a way that is not related to music,” he said of his study.
Citation: Landry, Simon P., and François Champoux. “Musicians react faster and are better multisensory integrators.” Brain and Cognition 111 (2017): 156-162. DOI: 10.1016/j.bandc.2016.12.001 Research funding: Canadian Institutes of Health Research, Fonds de recherche Québec – Santé, and Natural Sciences and Engineering Research Council of Canada. Adapted from press release by the Université de Montréal.
University of Arizona researchers discovered that MRI scans of endurance runners’ brains have greater functional connectivity than the brains of more sedentary individuals. Researchers compared brain scans of young adult cross country runners to young adults who don’t engage in regular physical activity. The runners, overall, showed greater functional connectivity or connections between distinct brain regions within several areas of the brain, including the frontal cortex, which is important for cognitive functions such as planning, decision-making and the ability to switch attention between tasks.
Although additional research is needed to determine whether these physical differences in brain connectivity result in differences in cognitive functioning, the current findings, published in the journal Frontiers in Human Neuroscience, help lay the groundwork for researchers to better understand how exercise affects the brain, particularly in young adults.
UA running expert David Raichlen, an associate professor of anthropology, co-designed the study with UA psychology professor Gene Alexander, who studies brain aging and Alzheimer’s disease as a member of the UA’s Evelyn F. McKnight Brain Institute. “One of the things that drove this collaboration was that there has been a recent proliferation of studies, over the last 15 years, that have shown that physical activity and exercise can have a beneficial impact on the brain, but most of that work has been in older adults,” Raichlen said.
“This question of what’s occurring in the brain at younger ages hasn’t really been explored in much depth, and it’s important,” he said. “Not only are we interested in what’s going on in the brains of young adults, but we know that there are things that you do across your lifespan that can impact what happens as you age, so it’s important to understand what’s happening in the brain at these younger ages.”
Along with their colleagues, Raichlen and Alexander compared the MRI scans of a group of male cross country runners to the scans of young adult males who hadn’t engaged in any kind of organized athletic activity for at least a year. Participants were roughly the same age — 18 to 25 — with comparable body mass index and educational levels. The scans measured resting state functional connectivity, or what goes on in the brain while participants are awake but at rest, not engaging in any specific task. The findings shed new light on the impact that running, as a particular form of exercise, may have on the brain.
Previous studies have shown that activities that require fine motor control, such as playing a musical instrument, or that require high levels of hand-eye coordination, such as playing golf, can alter brain structure and function. However, fewer studies have looked at the effects of more repetitive athletic activities that don’t require as much precise motor control such as running. Raichlen’s and Alexander’s findings suggest that these types of activities could have a similar effect.
“These activities that people consider repetitive actually involve many complex cognitive functions like planning and decision-making that may have effects on the brain,” Raichlen said.
Since functional connectivity often appears to be altered in aging adults, and particularly in those with Alzheimer’s or other neurodegenerative diseases, it’s an important measure to consider, Alexander said. And what researchers learn from the brains of young adults could have implications for the possible prevention of age-related cognitive decline later on.
“One of the key questions that these results raise is whether what we’re seeing in young adults in terms of the connectivity differences imparts some benefit later in life,” said Alexander, who also is a professor of neuroscience and physiological sciences. “The areas of the brain where we saw more connectivity in runners are also the areas that are impacted as we age, so it really raises the question of whether being active as a young adult could be potentially beneficial and perhaps afford some resilience against the effects of aging and disease.”
Citation: Raichlen, David A., Pradyumna K. Bharadwaj, Megan C. Fitzhugh, Kari A. Haws, Gabrielle-Ann Torre, Theodore P. Trouard, and Gene E. Alexander. “Differences in Resting State Functional Connectivity between Young Adult Endurance Athletes and Healthy Controls.” Frontiers in Human Neuroscience 10 (2016): 610. DOI: 10.3389/fnhum.2016.00610 Adapted from press release by University of Arizona.
Simon Fraser University researchers have found that high-resolution brain scans, coupled with computational analysis, could play a critical role in helping to detect concussions that conventional scans might miss.
In a study published in PLOS Computational Biology, Vasily Vakorin and Sam Doesburg show how magnetoencephalography (MEG), which maps interactions between regions of the brain, could detect greater levels of neural changes than typical clinical imaging tools such as MRI or CAT scans.
Qualified clinicians typically use those tools, along with other self-reporting measures such as headache or fatigue, to diagnose concussion. They also note that related conditions such as mild traumatic brain injury, often associated with football player collisions, don’t appear on conventional scans.
“Changes in communication between brain areas, as detected by MEG, allowed us to detect concussion from individual scans, in situations where MRI or CT failed,” says Vakorin. The researchers are scientists with the Behavioral and Cognitive Neuroscience Institute based at SFU, and SFU’s ImageTech Lab, a new facility at Surrey Memorial Hospital. Its research-dedicated magnetoencephalography (MEG) and MRI scanners make the lab unique in western Canada.
The researchers took magnetoencephalography (MEG) scans of 41 men between 20-44 years of age. Half had been diagnosed with concussions within the past three months.
They found that concussions were associated with alterations in the interactions between different brain areas–in other words, there were observable changes in how areas of the brain communicate with one another.
The researchers say magnetoencephalography (MEG) offers an unprecedented combination of “excellent temporal and spatial resolution” for reading brain activity to better diagnose concussion where other methods fail.
Relationships between symptom severity and magnetoencephalography (MEG) based classification also show that these methods may provide important measurements of changes in the brain during concussion recovery.
The researchers hope to refine their understanding of specific neural changes associated with concussions to further improve detection, treatment and recovery processes.
Citation:“Detecting Mild Traumatic Brain Injury Using Resting State Magnetoencephalographic Connectivity.” Vakorin, Vasily A., Sam M. Doesburg, Leodante da Costa, Rakesh Jetly, Elizabeth W. Pang, and Margot J. Taylor. PLOS Computational Biology 12, no. 12 (2016): e1004914. DOI: 10.1371/journal.pcbi.1004914 Research funding: Defense Research and Development Canada. Adapted from press release by Simon Fraser University.