Without their keen sense of smell, mosquitoes wouldn’t get very far. They rely on this sense to find a host to bite and spots to lay eggs.

And without that sense of smell, mosquitoes could not locate their dominant source of food: nectar from flowers.

“Nectar is an important source of food for all mosquitoes,” said , a professor of biology at the ����Ӱ�Ӵ�ý. “For male mosquitoes, nectar is their only food source, and female mosquitoes feed on nectar for all but a few days of their lives.”

Yet scientists know little about the scents that draw mosquitoes toward certain flowers, or repel them from others. This information could help develop less toxic and better repellents, more effective traps and understand how the mosquito brain responds to sensory information — including the cues that, on occasion, lead a female mosquito to bite one of us.

Riffell’s team, which includes researchers at the UW, Virginia Tech and UC San Diego, has discovered the chemical cues that lead mosquitoes to pollinate a particularly irresistible species of orchid. As they report in a published in the Proceedings of the National Academy of Sciences, the orchid produces a finely balanced bouquet of chemical compounds that stimulate mosquitoes’ sense of smell. On their own, some of these chemicals have either attractive or repressive effects on the mosquito brain. When combined in the same ratio as they’re found in the orchid, they draw in mosquitoes as effectively as a real flower. Riffell’s team also showed that one of the scent chemicals that repels mosquitoes lights up the same region of the mosquito brain as , a common and controversial mosquito repellant.

Their findings show how environmental cues from flowers can stimulate the mosquito brain as much as a warm-blooded host — and can draw the mosquito toward a target or send it flying the other direction, said Riffell, who is the senior author of the study.

The blunt-leaf orchid, or Platanthera obtusata, grows in cool, high-latitude climates across the Northern Hemisphere. From field stations in the Okanogan-Wenatchee National Forest in Washington state, Riffell’s team verified past research showing that local mosquitoes pollinate this species, but not its close relatives that grow in the same habitat. When researchers covered the flowers with bags — depriving the mosquitoes of a visual cue for the flower — the mosquitoes would still land on the bagged flowers and attempt to feed through the canvas.

Orchid scent obviously attracted the mosquitoes. To find out why, Riffell’s team turned to the individual chemicals that make up the blunt-leaf orchid’s scent.

“We often describe ‘scent’ as if it’s one thing — like the scent of a flower, or the scent of a person,” said Riffell. “Scent is actually a complex combination of chemicals — the scent of a rose consists of more than 300 — and mosquitoes can detect the individual types of chemicals that make up a scent.”

Riffell describes the blunt-leaf orchid’s scent as a grassy or musky odor, while its close relatives have a sweeter fragrance. The team used gas chromatography and mass spectroscopy to identify dozens of chemicals in the scents of the Platanthera species. Compared to its relatives, the blunt-leaf orchid’s scent contained high amounts of a compound called , and smaller amounts of another chemical, lilac aldehyde.

Riffell’s team also recorded the electrical activity in mosquito antennae, which detect scents. Both nonanal and lilac aldehyde stimulated antennae of mosquitoes that are native to the blunt-leaf orchid’s habitat. But these compounds also stimulated the antennae of mosquitoes from other regions, including Anopheles stephensi, which spreads malaria, and Aedes aegypti, which spreads dengue, yellow fever, Zika and other diseases.

Experiments of mosquito behavior showed that both native and non-native mosquitoes preferred a solution of nonanal and lilac aldehyde mixed in the same ratio as found in blunt-leaf flowers. If the researchers omitted lilac aldehyde from the recipe, mosquitoes lost interest. If they added more lilac aldehyde — at levels found in the blunt-leaf orchid’s close relatives — mosquitoes were indifferent or repelled by the scent.

Using techniques developed in Riffell’s lab, they also peered directly into the brains of Aedes increpitus mosquitoes, which overlap with blunt-leaf orchids, and a genetically modified strain of Aedes aegypti by Riffell and co-author , an associate professor at UC San Diego. They imaged calcium ions — signatures of actively firing neurons — in the antenna lobe, the region of the mosquito brain that processes signals from the antennae.

These brain imaging experiments revealed that nonanal and lilac aldehyde stimulate different parts of the antenna lobe — and even compete with one another when stimulated: The region that responds to nonanal can suppress activity in the region that responds to lilac aldehyde, and vice versa. Whether this “cross talk” makes a flower attractive or repelling to the mosquito likely depends on the amounts of nonanal and lilac aldehyde in the original scent. Blunt-leaf orchids have a ratio that attracts mosquitoes, while closely related species do not, according to Riffell.

“Mosquitoes are processing the ratio of chemicals, not just the presence or absence of them,” said Riffell. “This isn’t just important for flower discrimination — it’s also important for how mosquitoes discern between you and I. Human scent is very complex, and what is probably important for attracting or repelling mosquitoes is the ratio of particular chemicals. We know that some people get bit more than others, and maybe a difference in ratio explains why.”

The team also discovered that lilac aldehyde stimulates the same region of the antenna lobe as DEET. That region may process “repressive” scents, though further research would need to verify this, said Riffell. It’s too soon to tell if lilac aldehyde may someday be an effective mosquito repellant. But if it is, there is an added bonus.

“It smells wonderful,” said Riffell.

Lead author is , who conducted the research as a UW postdoctoral fellow and is now a research assistant professor at Virginia Tech. Additional co-authors are , a former UW postdoctoral researcher and current assistant professor at Virginia Tech; UW biology graduate students and ; and UW postdoctoral researcher . The research was funded by the National Institutes of Health, the Air Force Office of Scientific Research and the ����Ӱ�Ӵ�ý.

For more information, contact Riffell at 206-685-2573 or jriffell@uw.edu.

Gift brings Weill Family Foundation philanthropic giving in neuroscience to over $300 million, enabling bold approaches to curing these diseases

With a $106 million gift from the Weill Family Foundation, UC Berkeley, UC San Francisco and the ����Ӱ�Ӵ�ý have launched the , an innovative research network that will forge and nurture new collaborations between neuroscientists and researchers working in an array of other disciplines — including engineering, computer science, physics, chemistry and mathematics — to speed the development of new therapies for diseases and disorders that affect the brain and nervous system.

A 2016 study by the Information Technology & Innovation Foundation estimated that, in the U.S. alone, neurological and psychiatric disorders and diseases — including Alzheimer’s; Parkinson’s; anxiety and depression; traumatic brain injury and spinal cord injury; multiple sclerosis; ALS; and schizophrenia — carry an economic cost of more than $1.5 trillion per year, nearly 9 percent of GDP.

“The gains in knowledge amassed by neuroscientists over the past few decades can now be brought to the next level with supercomputers, electronic brain–computer interfaces, nanotechnology, robotics and powerful imaging tools,” said philanthropist Sanford I. “Sandy” Weill, chairman of the Weill Family Foundation. “The Neurohub will seize this opportunity by building bridges between people with diverse talents and training and bringing them together in a common cause: discovering new treatments to help the millions of patients with such conditions as Alzheimer’s disease and mental illness.”

Complementing the strengths of UCSF, Berkeley and the UW, the Weill Neurohub will draw on the expertise and resources of the 17 National Laboratories overseen by the Department of Energy, which excel in bioengineering, imaging, and data science. In August 2019, the Weill Family Foundation and the DOE signed a Memorandum of Understanding creating a new public–private partnership. The partnership is exploring the use of the Department’s artificial intelligence and supercomputing capabilities, in conjunction with Bay Area universities and the private sector, to advance the study of traumatic brain injury, or TBI, and neurodegenerative diseases.

Secretary of Energy Rick Perry, who has spearheaded the creation of an AI and Technology Office during his tenure at DOE, said that the vision for the Weill Neurohub dovetails with his own mission to make publicly funded AI and supercomputing resources more widely accessible to advance scientific discovery. “We are on the cusp of great discoveries that could transform our approach to TBI, Alzheimer’s disease and other neurological and psychiatric disorders, and easing access to the world-class computational power of our National Laboratories to initiatives like the Weill Neurohub is a win-win for science and the public sector — and, eventually, for patients.”

As many neurological disorders, such as dementia, are associated with aging, the costs of these unmet medical needs are expected to increase significantly in the coming years. California, with the largest aging population in the U.S., with one in five residents reaching age 65 or older in the next decade, faces particularly formidable challenges, said Gov. Gavin Newsom.

“Every day, millions of people in California, the nation, and the world are facing the uncertainty of neuro-related diseases, mental illness and brain injuries, and collaboration between different disciplines in science, academia, government and philanthropy is critical to meet this challenge. Together, we must accelerate the development and use cutting-edge technology, innovation and tools that will advance research and practical application that will benefit people across the world and for generations to come,” said Newsom. “I want to thank Sandy Weill and his wife, Joan, for their amazing work, kindness, dedication and commitment to philanthropic causes, especially when they open doors, bridge gaps, and make innovation and collaboration possible to advance causes that can truly have an impact on people’s quality of life.”

The Weill Neurohub will enable the three universities to work together on these pressing problems. For example, the UW and UCSF, renowned research universities with long traditions of excellence in basic neuroscience research, also have federally sponsored Alzheimer’s Disease Research Centers, or ADRCs. Through the Weill Neurohub, members of the UW’s ARDC, part of the UW Medicine Memory and Brain Wellness Center, and UCSF’s ADRC, led by the UCSF Memory and Aging Center, will collaborate with top neurodegeneration researchers at Berkeley.

The Weill Neurohub will provide funding for faculty, postdoctoral fellows, and graduate students at the UW, Berkeley and UCSF working on cross-disciplinary projects, including funding for “high-risk/high-reward” proposals that are particularly innovative and less likely to find support through conventional funding sources. But the bulk of the Weill Neurohub’s funding will support highly novel cross-institutional projects built on one or more of four scientific “pillars” that Weill Neurohub leaders have deemed priority areas for answering the toughest questions about the brain and discovering new approaches to disease: imaging; engineering; genomics and molecular therapeutics; and computation and data analytics.

The Weill Neurohub may seek additional academic, corporate and philanthropic partners to harness resources collaboratively, better scale research and development efforts, share information and data and create partnerships to make breakthroughs faster and at a lower cost than the current paradigm allows.

Relevant examples of interdisciplinary or cross-institutional neuroscience projects now underway at UCSF, Berkeley and/or the UW include:

• Design and construction of “NextGen7T” MRI brain scanner technology, which will shatter current resolution limits, creating the world’s first clear images of brain structures as small as 200 to 300 microns — a quarter of the size of a grain of sand — which is about 60 times sharper than a standard hospital MRI. For brain function, NextGen7T will be able to detect activity in regions as small as 400 microns, allowing for the discovery of new brain circuits and, for the first time, detecting the direction of information flow in the brain. This breakthrough tool will provide Weill Neurohub investigators with deeper understanding of how brain structure and function change in disease, and to test the effectiveness of treatment innovations.
• Customized neurotherapies based on the CRISPR gene-targeting system to treat rare inherited movement disorders and eye diseases that can lead to blindness.
• Implants that read and decode brain signals that could allow paralyzed patients to easily control robotic limbs or exoskeletons, restoring their ability to use objects or walk; similar implants are under study to restore speech in stroke patients, to reduce chronic pain, and to treat severe, intractable depression and anxiety.
• Miniaturized, non-invasive Band-Aid–sized devices that could provide therapeutic stimulation through the skin to treat spinal cord injury.
• AI applications with the power to detect tiny but life-threatening hemorrhages in CT scans of the entire brain, which may contain over a million pixels, in minutes. With this information, neuroradiologists can quickly consult with neurologists and neurosurgeons, when time is of the essence, to zero in on the best treatment plan.
• Tablet-based applications that seamlessly draw together medical records, images and population-derived data, giving patients with neurological diseases such as multiple sclerosis an easy-to-use portal to record, analyze and understand their health.

This gift expands on the unique vision and mission of the UCSF Weill Institute for Neurosciences, established in 2016 with a $185 million gift from the Weill Family Foundation and Joan and Sandy Weill — whose giving to the neuroscience community now exceeds $300 million — said UCSF’s Dr. , the Robert A. Fishman Distinguished Professor of Neurology and Weill Institute director.

“The UCSF Weill Institute set out to break down walls between the clinical disciplines of neurology, neurosurgery and psychiatry, and also bring these clinical specialties together with the basic neurosciences,” said Hauser. “Now, with the Weill Neurohub, we’re going even further: eliminating institutional boundaries between three great public research universities, and also other disciplinary walls between ‘traditional’ neuroscience and ‘non-traditional’ approaches to understanding the brain. By embracing engineering, data analysis and imaging science at this dramatically higher level — areas in which both Berkeley and the UW are among the best in the world — neuroscientists on all three campuses will gain crucial tools and insights that will bring us closer to our shared goal of reducing suffering from brain diseases.”

Hauser will serve as one of two co-directors of the new Weill Neurohub along with Berkeley’s , the Evan Rauch Chair of Neuroscience. Together with , the Joan and Richard Komen Endowed Chair and professor of biology at the UW, they will serve on the Weill Neurohub’s Leadership Committee.

“In the Weill Neurohub, the emphasis will be on technology to enable discovery of disease mechanisms, and thus development of novel treatments and early detection of neurologic diseases, to allow intervention before conditions become severe,” said Isacoff, who heads Berkeley’s Helen Wills Neuroscience Institute. “The technologies include next-generation neuroimaging and therapeutic manipulations ranging from brain implants to CRISPR gene editing, with major efforts in machine learning and high-speed computation. I think these three campuses can succeed in this joint mission in a way that no others can — the combined expertise this group brings to the table, especially when you bring in the National Labs, really is unparalleled.”

The UW’s Daniel added, “The Weill Neurohub brings together three outstanding public institutions, each with a deep commitment to bridge boundaries between science, engineering, computer science and data science to address fundamental problems in neuroscience and neural disorders. To my knowledge, this is a nationally unique enterprise — drawing on diverse approaches to accomplish goals no single institution could reach alone, as well as seeding and accelerating research and discovery.”

Neuroscientists have made huge strides in understanding the brain in the 30 years since President George H. W. Bush designated the 1990s as the “Decade of the Brain,” and subsequently through the National Institute of Health’s ongoing BRAIN Initiative, first announced by President Obama in 2013. But treatments for neurological and psychiatric diseases have lagged far behind those for other common afflictions, such as cardiovascular disease and cancer.

Much of the lack of progress on neurological and psychiatric disease is due to the unparalleled complexity of the nervous system, in which hundreds of billions of nerve cells and support cells form as many as 100 trillion connections in intricate three-dimensional networks throughout the brain and spinal cord. The Weill Neurohub’s leaders believe reaching beyond conventional approaches is essential to grappling with this complexity.

“Despite amazing advances in neuroscience, new therapies are not reaching patients with mental illness and neurological disorders nearly as quickly as they have for heart disease and cancer. And in addition to the terrible personal toll these illnesses exact on patients and their families, they also have a massive impact on our healthcare system and on the global economy,” said Joan Weill, president of the Weill Family Foundation. “Our goal, through the broad and multifaceted approach of the Weill Neurohub, is to begin to change that.”

Through behavioral experiments and real-time recording of the female mosquito brain, a team of scientists, led by researchers at the ����Ӱ�Ӵ�ý, has discovered how the mosquito brain integrates signals from two of its sensory systems — visual and olfactory — to identify, track and hone in on a potential host for her next blood meal.

Their findings, July 18 in the journal , indicate that, when the mosquito’s olfactory system detects certain chemical cues, they trigger changes in the mosquito brain that initiate a behavioral response: The mosquito begins to use her visual system to scan her surroundings for specific types of shapes and fly toward them, presumably associating those shapes with potential hosts.

Only female mosquitoes feed on blood, and these results give scientists a much-needed glimpse of the sensory-integration process that the mosquito brain uses to locate a host. Scientists can use these findings to help develop new methods for mosquito control and reduce the spread of mosquito-borne diseases.

This study focused on the olfactory cue that triggers the hunt for a host: carbon dioxide, or CO2. For mosquitoes, smelling CO2 is a telltale sign that a potential meal is nearby.

“Our breath is just loaded with CO2,” said corresponding author , a UW professor of biology. “It’s a long-range attractant, which mosquitoes use to locate a potential host that could be more than 100 feet away.”

That potential host could be a person or another warm-blooded animal. Prior research by Riffell and his collaborators has shown that smelling CO2 can “prime” the mosquito’s visual system to hunt for a host. In this new research, they measure how CO2 triggers precise changes in mosquito flight behavior and visualize how the mosquito brain responds to combinations of olfactory and visual cues.

The team collected data from approximately 250 individual mosquitoes during behavioral trials conducted in a small circular arena, about 7 inches in diameter. A 360-degree LED display framed the arena and a tungsten wire tether in the middle held each mosquito. An optical sensor below the insect collected data about mosquito wingbeats, an air inlet and vacuum line streamed odors into the arena, and the LED display showed different types of visual stimuli.

The team tested how tethered mosquitoes responded to visual stimuli as well as puffs of CO2-rich air. They found that, in the arena, one-second puffs of air containing 5% CO2 — just above the 4.5% CO2 air emitted by humans — prompted the mosquitoes to beat their wings faster. Some visual elements like a fast-moving starfield had little effect on mosquito behavior. But if the arena showed a horizontally moving bar, mosquitoes beat their wings faster and attempted to steer in the same direction. This response was more pronounced if researchers introduced a puff of CO2 before showing the bar.

To get a clear picture of how smelling CO2 first affected flight behavior, they analyzed their data using a mathematical model of housefly flight behavior.

“We found that CO2 influences the mosquito’s ability to turn toward an object that isn’t directly in their flight path,” said Riffell. “When they smell the CO2, they essentially turn toward the object in their visual field faster and more readily than they would without CO2.”

The researchers repeated the arena experiments with created by Riffell and co-author , an assistant professor at the University of California, San Diego. Cells in these mosquitoes glow fluorescent green if they contain high levels of calcium ions — including neurons of the central nervous system when they are actively firing. In the arena, the researchers removed a small portion of the mosquito skull and used a microscope to view neuronal activity in sections of the brain in real time.

The team focused on 59 “regions of interest” that showed especially high levels of calcium ion levels in the lobula, a part of the mosquito brain’s optic lobe. If the mosquito was shown a horizontal bar, two-thirds of those regions lit up, indicating increased neuronal firing in response to the visual stimulus. When the researchers introduced a puff of CO2 first and then showed the horizontal bar, 23% of the regions had even higher activity than before — indicating that the CO2 odor prompted a larger-magnitude response in these areas of the brain that control vision.

The researchers tried the reverse experiment — seeing if a horizontal bar triggered increased firing in the parts of the mosquito brain that control smell — but saw no response.

“Smell triggers vision, but vision does not trigger the sense of smell,” said Riffell.

Their findings align with the general picture of mosquito senses. The mosquito sense of smell operates at long distances, picking up scents more than 100 feet away. But their eyesight is most effective for objects 15 to 20 feet away, according to Riffell.

“Olfaction is a long-range sense for mosquitoes, while vision is for intermediate-range tracking,” said Riffell. “So, it makes sense that we see an odor — in this case CO2 — affecting parts of the mosquito brain that control vision, and not the reverse.”

In the future, Riffell wants to test whether other shapes affect mosquito behavior and activity in the optic lobe. Those results may further illuminate the hierarchical nature of mosquito host-hunting behaviors: smell first, then see. It may also provide new knowledge for mosquito control.

Co-lead authors on the paper are former UW postdoctoral researchers , now an assistant professor at Virginia Tech, and , now an assistant professor at the University of Nevada-Reno. Additional co-authors include UW alumna Lauren Locke; UW undergraduate student Kennedy Tobin; , a professor at Caltech; and , a UW professor of physiology and biophysics. The research was funded by the Air Force Office of Scientific Research, the National Institutes of Health and the ����Ӱ�Ӵ�ý.

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For more information, contact Riffell at jriffell@uw.edu or van Breugel at fvanbreugel@unr.edu.

Grant numbers: FA9550-14-1-0398, FA9550-16-1-0167, 1RO1DCO13693, 1R21AI137947, 5K22AI113060, 1R21AI123937.

Over the past few years, scientists have faced a problem: They often cannot reproduce the results of experiments done by themselves or their peers.

This “” plagues fields from medicine to physics, and likely has many causes. But one is undoubtedly the difficulty of sharing the vast amounts of data collected and analyses performed in so-called “big data” studies.  The volume and complexity of the information also can make these scientific endeavors unwieldy when it comes time for researchers to share their data and findings with peers and the public.

Researchers at the ����Ӱ�Ӵ�ý have developed a set of tools to make one critical area of big data research — that of our central nervous system — easier to share. In a published online March 5 in , the UW team describes an open-access browser they developed to display, analyze and share neurological data collected through a type of magnetic resonance imaging study known as diffusion-weighted MRI.

“There has been a lot of talk among researchers about the replication crisis,” said lead author . “But we wanted a tool — ready, widely available and easy to use — that would actually help fight the replication crisis.”

Yeatman — who is an assistant professor in the UW Department of Speech & Hearing Sciences and the Institute for Learning & Brain Sciences () — is describing . This web browser-based tool, freely available online, is a platform for uploading, visualizing, analyzing and sharing diffusion MRI data in a format that is publicly accessible, improving transparency and data-sharing methods for neurological studies. In addition, since it runs in the web browser, AFQ-Browser is portable — requiring no additional software package or equipment beyond a computer and an internet connection.

“One major barrier to data transparency in neuroscience is that so much data collection, storage and analysis occurs on local computers with special software packages,” said senior author , a senior data scientist in the UW . “But using AFQ-Browser, we eliminate those requirements and make uploading, sharing and analyzing diffusion-weighted MRI data a simple, straightforward process.”

Diffusion-weighted MRI measures the movement of fluid in the brain and spinal cord, revealing the structure and function of white-matter tracts. These are the connections of the central nervous system, tissue that are made up primarily of axons that transmit long-range signals between neural circuits. Diffusion MRI research on brain connectivity has fundamentally changed the way neuroscientists understand human brain function: The state, organization and layout of white matter tracts are at the core of cognitive functions such as memory, learning and other capabilities. Data collected using diffusion-weighted MRI can be used to diagnose complex neurological conditions such as multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). Researchers also use diffusion-weighted MRI data to study the neurological underpinnings of conditions such as dyslexia and learning disabilities.

“This is a widely-used technique in neuroscience research, and it is particularly amenable to the benefits that can be gleaned from big data, so it became a logical starting point for developing browser-based, open-access tools for the field,” said Yeatman.

The AFQ-Browser — the AFQ stands for Automated Fiber-tract Quantification — can receive diffusion-weighted MRI data and perform tract analysis for each individual subject. The analyses occur via a remote server, again eliminating technical and financial barriers for researchers. The AFQ-Browser also contains interactive tools to display data for multiple subjects — allowing a researcher to easily visualize how white matter tracts might be similar or different among subjects, identify trends in the data and generate hypotheses for future experiments.

Researchers also can insert additional code to analyze the data, as well as save, upload and share data instantly with fellow researchers.

“We wanted this tool to be as generalizable as possible, regardless of research goals,” said Rokem. “In addition, the format is easy for scientists from a variety of backgrounds to use and understand — so that neuroscientists, statisticians and other researchers can collaborate, view data and share methods toward greater reproducibility.”

Embedded demo of AFQ-Browser

The idea for the AFQ-Browser came out of a UW course on data visualization, and the researchers worked with several graduate students to develop and perfect the browser. They tested it on existing diffusion-weighted MRI datasets, including research subjects with and . In the future, they hope that the AFQ-Browser can be improved to do automated analyses — and possibly even diagnoses — based on diffusion-weighted MRI data.

“AFQ-Browser is really just the start of what could be a number of tools for sharing neuroscience data and experiments,” said Yeatman. “Our goal here is greater reproducibility and transparency, and a more robust scientific process.”

Co-authors on the paper are UW physics doctoral student Adam Richie-Halford, UW chemical engineering doctoral student Josh Smith, and Anisha Keshavan, a UW postdoctoral researcher in I-LABS, the Institute for Neuroengineering, and the eScience Institute. The research was funded by the Gordon and Betty Moore Foundation, the Alfred P. Sloan Foundation and the U.S. Department of Energy.

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For more information, contact Yeatman at jyeatman@uw.edu or Rokem at arokem@gmail.com.

Most of us surely don’t think of mosquitoes as being especially adept at learning. But that may not be the case.

In a published Jan. 25 in , ����Ӱ�Ӵ�ý researchers report that mosquitoes can in fact learn to associate a particular odor with an unpleasant mechanical shock akin to being swatted. As a result, they’ll avoid that scent the next time.

“Once mosquitoes learned odors in an aversive manner, those odors caused aversive responses on the same order as responses to DEET, which is one of the most effective mosquito repellents,” said senior author , a UW professor of biology. “Moreover, mosquitoes remember the trained odors for days.”

Researchers already knew that mosquitoes don’t decide whom to bite at random. They show obvious preferences for some people over others. They are also known to alternate hosts seasonally, feeding on birds in the summer and mammals and birds during other parts of the year, for instance. Riffell and his colleagues wanted to find out more about how learning might influence mosquitoes’ biting preferences.

As a first step, they trained mosquitoes by pairing the odor of a particular person or animal species — a rat versus a chicken, for example — with a mechanical shock. For the mechanical shock, they used a vortex mixer to simulate the vibrations and accelerations a mosquito might experience when a person tried to swat them. The insects quickly learned the association between the host odor and the mechanical shock and used that information in deciding which direction to fly — though interestingly, the mosquitoes could never learn to avoid the smell of a chicken.

Learning in many animals, from honeybees to humans, depends on dopamine in the brain. Additional experiments by Riffell and his team showed that dopamine also is essential in mosquito learning. Genetically modified mosquitoes lacking dopamine receptors lost the ability to learn.

The researchers also glued mosquitoes to a custom, 3-D-printed miniature “arena” in which the insects could fly in place, while researchers recorded the activity of neurons in the olfactory center of their brains. Those experiments showed that without dopamine, those neurons were less likely to fire. As a result, mosquitoes became less able to process and learn from odor information.

These findings may have important implications for mosquito control and the transmission of mosquito-borne diseases, according to the researchers.

“By understanding how mosquitoes are making decisions on whom to bite, and how learning influences those behaviors, we can better understand the genes and neuronal bases of the behaviors,” said Riffell. “This could lead to more effective tools for mosquito control.”

With this new understanding of how mosquitoes learn to avoid certain hosts, the researchers say they are now exploring mosquitoes’ ability to learn and remember favored hosts.

“In both cases, we think dopamine is a critical component,” said Riffell.

Co-lead authors on the paper are former UW postdoctoral researchers and . Vinauger is now an assistant professor of biochemistry at Virginia Tech, and Lahondère is a research assistant professor of biochemistry at Virginia Tech. UW co-authors are postdoctoral researcher Gabriella Wolff, undergraduate alumna Lauren Locke, undergraduate Jessica Liaw and associate professor of biology . Additional co-authors are assistant professor of the University of California, Riverside and professor of the California Institute of Technology.

The research was funded by the Air Force Office of Sponsored Research; the National Institutes of Health; the National Science Foundation; the University of California, Riverside; MaxMind; a UW Endowed Professorship for Excellence in Biology; the UW ; and the .

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For more information, contact Riffell at jriffell@uw.edu or Vinauger at vinauger@vt.edu.

Adapted from a by Current Biology.

Grant numbers: FA9550-14-1-0398, FA9550-16-1-0167, NIH1RO1DCO13693-0, IOS-1354159, HFSP-RGP0022.

When those children come from low-income households with limited English proficiency, there can be significant barriers in getting them the care they need.

A recent ����Ӱ�Ӵ�ý found that less than 20 percent of rehabilitation providers in the state accepted Medicaid and also provided language interpretation to children with traumatic brain injuries. Just 8 percent provided mental health services to those children, and Spanish-speaking families had to travel significantly further to access services.

The findings highlight how already disadvantaged children are further impacted by limited access to the rehabilitation services that vastly improve long-term outcomes, said lead author , the Sidney Miller Endowed Assistant Professor in Direct Practice at the UW School of Social Work and a core faculty member at the UW .

“Rehabilitation after a brain injury is incredibly important, especially for kids with moderate to severe brain injuries,” Moore said. “Ultimately, that limited availability is going to impact children’s outcomes.”

For the study, published in the in March, the researchers compiled a database of 293 health providers around Washington offering physical and occupational therapy; speech, language and cognitive therapy; and mental health services. A research assistant called each provider and asked about the types of services offered, whether Medicaid was accepted and if interpretation was available for non-English-speaking families.

The research found that:

• Only 46 percent of providers accepted children with Medicaid
• Children covered by Medicaid had fewer rehabilitation services available than those covered by private insurance
• In each of the three general areas of health care listed above, there were fewer services for children whose families needed language interpretation
• While mental health services comprised more than half of the rehabilitation services available, only 8 percent of those providers accepted children with Medicaid who needed language services
• Less than half of the physical and occupational services accepted children with Medicaid and provided language services
• In total, less than 20 percent of all providers accepted children with Medicaid and also provided language services

The researchers also looked at travel times for 82 children with moderate to severe traumatic brain injuries who were treated at Harborview Medical Center, using data from a study. They found that regardless of their child’s insurance status, Spanish-speaking parents had to drive an average of 16 minutes more than English-speaking parents to reach a mental health provider, and they had to travel an additional nine minutes to get to physical, occupational, speech and cognitive therapy.

The study found that more diverse counties also had fewer multilingual rehabilitation services — for every 10 percent increase in of non-English speakers over the age of 5 at home, there was a 34 percent drop in the availability of those services.

The inequities may be even greater than the study shows, the researchers note, since providers who accept Medicaid may routinely limit the number of Medicaid-covered children that they accept, due to lower reimbursement rates.

The study follows earlier UW which found disparities in outcomes among Latino children after traumatic brain injuries. The researchers wondered whether the disparities might have to do with a lack of rehabilitation services generally, but instead identified an access issue for low-income children from families with limited English proficiency.

That gap is particularly worrisome given the state’s increasing diversity — more than 18 percent of households in Washington spoke a language other than English in 2012, the study notes, and almost half of children younger than 18 had Medicaid insurance in 2011.

Joana Ramos, co-chair of the , said advocates regularly hear that families are being turned away from health care providers or being required to provide their own interpreters.

“It’s a huge problem, and we definitely need to get everybody on board to address it, not just the advocates,” she said. “Language services need to be a routine part of health care services, not a standalone thing.”

Moore said since the bulk of rehabilitation after a brain injury takes place in the community, workers at the hospitals where children are initially treated should try to connect parents with services before they leave.

“We need to be thinking more critically about how we transition kids back to the community, particularly children we know have limited access to services,” she said. “We really have to do a thorough job of linking them to these services on the outpatient side.

“Knowing what we know now, it’s a social justice obligation.”

The research was funded by the National Center for Advancing Translational Sciences of the National Institutes of Health and the National Institute of Child Health and Human Development.

Co-authors are , an anesthesiologist at Children’s Hospital; , an assistant professor of epidemiology at the UW School of Public Health; , a graduate student at Boston College; Kate Baron, a research assistant at Harborview Injury Prevention Center; , director of support programs at the Brain Injury Alliance of Washington; , executive director of the Brain Injury Alliance of Washington; , professor and vice president of academic affairs at the UW Department of Pediatrics; , a professor of rehabilitation medicine and adjunct professor of pediatrics and neurological surgery at UW Medicine; and , a UW professor of pediatrics.

For more information, contact Moore at mm99@uw.edu or 206-616-2862.

Imagine a question-and-answer game played by two people who are not in the same place and not talking to each other. Round after round, one player asks a series of questions and accurately guesses the object the other is thinking about.

Sci-fi? Mind-reading superpowers? Not quite.

����Ӱ�Ӵ�ý researchers recently used a direct brain-to-brain connection to enable pairs of participants to play a question-and-answer game by transmitting signals from one brain to the other over the Internet. The experiment, detailed today in , is thought to be the first to show that two brains can be directly linked to allow one person to guess what’s on another person’s mind.

“This is the most complex brain-to-brain experiment, I think, that’s been done to date in humans,” said lead author , an assistant professor of psychology and a researcher at UW’s .

“It uses conscious experiences through signals that are experienced visually, and it requires two people to collaborate,” Stocco said.

Here’s how it works: The first participant, or “respondent,” wears a cap connected to an (EEG) machine that records electrical brain activity. The respondent is shown an object (for example, a dog) on a computer screen, and the second participant, or “inquirer,” sees a list of possible objects and associated questions. With the click of a mouse, the inquirer sends a question and the respondent answers “yes” or “no” by focusing on one of two flashing LED lights attached to the monitor, which flash at different frequencies.

A “no” or “yes” answer both send a signal to the inquirer via the Internet and activate a magnetic coil positioned behind the inquirer’s head. But only a “yes” answer generates a response intense enough to stimulate the visual cortex and cause the inquirer to see a flash of light known as a “.” The phosphene — which might look like a blob, waves or a thin line — is created through a brief disruption in the visual field and tells the inquirer the answer is yes. Through answers to these simple yes or no questions, the inquirer identifies the correct item.

The experiment was carried out in dark rooms in two UW labs located almost a mile apart and involved five pairs of participants, who played 20 rounds of the question-and-answer game. Each game had eight objects and three questions that would solve the game if answered correctly. The sessions were a random mixture of 10 real games and 10 control games that were structured the same way.

The researchers took steps to ensure participants couldn’t use clues other than direct brain communication to complete the game. Inquirers wore earplugs so they couldn’t hear the different sounds produced by the varying stimulation intensities of the “yes” and “no” responses. Since noise travels through the skull bone, the researchers also changed the stimulation intensities slightly from game to game and randomly used three different intensities each for “yes” and “no” answers to further reduce the chance that sound could provide clues.

The researchers also repositioned the coil on the inquirer’s head at the start of each game, but for the control games, added a plastic spacer undetectable to the participant that weakened the magnetic field enough to prevent the generation of phosphenes. Inquirers were not told whether they had correctly identified the items, and only the researcher on the respondent end knew whether each game was real or a control round.

“We took many steps to make sure that people were not cheating,” Stocco said.

Participants were able to guess the correct object in 72 percent of the real games, compared with just 18 percent of the control rounds. Incorrect guesses in the real games could be caused by several factors, the most likely being uncertainty about whether a phosphene had appeared.

“They have to interpret something they’re seeing with their brains,” said co-author , a faculty member at the and a UW associate professor of psychology. “It’s not something they’ve ever seen before.”

Errors can also result from respondents not knowing the answers to questions or focusing on both answers, or by the brain signal transmission being interrupted by hardware problems.

“While the flashing lights are signals that we’re putting into the brain, those parts of the brain are doing a million other things at any given time too,” Prat said.

The study builds on the UW team’s in 2013, when it was the first to demonstrate a direct brain-to-brain connection between humans. Other scientists have connected the brains of rats and monkeys, and transmitted brain signals from a human to a rat, using electrodes inserted into animals’ brains. In the 2013 experiment, the UW team used noninvasive technology to send a person’s brain signals over the Internet to control the hand motions of another person.

The experiment evolved out of research by co-author , a UW professor of computer science and engineering, on that enable people to activate devices with their minds. In 2011, Rao began collaborating with Stocco and Prat to determine how to link two human brains together.

In 2014, the researchers received a $1 million grant from the that allowed them to broaden their experiments to decode more complex interactions and brain processes. They are now exploring the possibility of “brain tutoring,” transferring signals directly from healthy brains to ones that are developmentally impaired or impacted by external factors such as a stroke or accident, or simply to transfer knowledge from teacher to pupil.

The team is also working on transmitting brain states — for example, sending signals from an alert person to a sleepy one, or from a focused student to one who has attention deficit hyperactivity disorder, or ADHD.

“Imagine having someone with ADHD and a neurotypical student,” Prat said. “When the non-ADHD student is paying attention, the ADHD student’s brain gets put into a state of greater attention automatically.”

Many technological advancements over the past century, from the telegraph to the Internet, were created to facilitate communication between people. The UW team’s work takes a different approach, using technology to strip away the need for such intermediaries.

“Evolution has spent a colossal amount of time to find ways for us and other animals to take information out of our brains and communicate it to other animals in the forms of behavior, speech and so on,” Stocco said. “But it requires a translation. We can only communicate part of whatever our brain processes.

“What we are doing is kind of reversing the process a step at a time by opening up this box and taking signals from the brain and with minimal translation, putting them back in another person’s brain,” he said.

Other co-authors are UW computer science and neurobiology undergraduate student , UW bioengineering doctoral student Jeneva Cronin, UW bioengineering doctoral student Joseph Wu, and , a research assistant at the UW Institute for Learning & Brain Sciences.

That research has focused largely on “” that show how certain parts of the brain correspond point-for-point with the body’s topography. These body maps have been studied extensively in adult humans and other primates, but how they develop in babies, and how they relate to other aspects of infant development, have been little understood.

Researchers at the ����Ӱ�Ӵ�ý’s (I-LABS) are among the first scientists worldwide to study body maps in the infant brain.

In a published in the September issue of Trends in Cognitive Sciences, Peter Marshall and Andrew Meltzoff argue that this new area of infant neuroscience can provide crucial information about how babies develop a sense of their physical selves, and can further understanding of how their earliest social relationships with others are formed.

“Body maps in the brain are an important part of how we build up an implicit sense of ourselves through the sense of having a body and seeing and feeling our bodies move,” said , lead author and professor of psychology at Temple University. “We also believe that these maps facilitate the connections that we build with other people, even in the early months of life.”

The article builds on previous studies conducted by Marshall and co-author, I-LABS co-director, which examined the properties of body maps in the infant brain. In one experiment, 7-month-old babies wore caps fitted with sensors that record brain activity by picking up tiny electrical signals from the surface of the head, a method known as electroencephalography, or EEG. The found that touches to infants’ hands and feet resulted in different patterns of activity in the part of the brain that processes touch.

The results showed that, much as in adults, the body maps of infants are organized in a particular way, though there is still much to learn about how the details of these maps are established in the developing brain.

Another using EEG showed that body maps in the infant brain are also activated by seeing other people carrying out actions with different parts of the body. Fourteen-month-olds were randomly assigned to watch an adult touch an object using either a hand or foot.

The pattern of infants’ brain activity corresponded to the body parts being used, providing the first evidence that watching someone else use a specific body part prompts a corresponding pattern of activity in the infant neural body map.

The researchers say this finding may advance understanding of the neural processes underlying imitation, an important means of learning for babies.

“This neuroscience work is helping us to understand the building blocks of infant learning,” Meltzoff said. “Before language, infants learn many skills and social customs by imitating others. Infants need to map the behaviors they see onto their own bodies in order to imitate. Understanding neural body maps may help explain how infants learn so rapidly from watching others in their culture.”

Taken together, the researchers say, the findings demonstrate that body maps develop early in life and may be integral for fostering infants’ sense of their own bodies, as well as the ability to connect with and learn from other people.

“We think this connection happens very early in development and allows infants to get a sense that other people are like them, because they move in similar ways,” said Marshall, who recently spent a year at I-LABS working closely with Meltzoff.

Similar research involving multiple parts of the body, the researchers write, is needed to build a more complete picture of how body maps develop in babies. There is some evidence that infants’ neural responses to hand stimulation change as they learn to grasp and reach for objects, they note. But how those neural pathways might shift as babies grow and develop is unknown.

Marshall noted the potential for a new area of study on the plasticity — the brain’s ability to change as a result of experience — of body maps in the developing brain. That research, he said, would “bring other key questions into focus, including how these maps may have their origins in fetal movements prior to birth.”

Most importantly, Marshall said, a deeper understanding of body maps in infants could help address one of the most complex questions in psychology: How do patterns of brain activity relate to cognitive and social development?

“One of the big challenges in psychology is to make meaningful connections across brain, behavior and cognitive and social processes,” he said. “Body maps are valuable because they’re on the surface of the brain, and signals from them are easily picked up and analyzed. “They might be an ideal area from which to pursue these larger questions — a sort of model for integration.”

The authors’ work is supported by the National Science Foundation and the National Institutes of Health.

These aggravating bites can also be conduits for hitchhiking pathogens to worm their way into our bodies. Mosquitoes spread malaria, dengue, yellow fever and West Nile virus, among others. As the bloodsucking insects evolve to resist our best pesticides, mosquito control may shift more to understanding how the mosquitoes find a tasty — and unsuspecting — human host.

A team of biologists from the ����Ӱ�Ӵ�ý and the has cracked the cues mosquitoes use to find us. As they report in a paper in , the minute insects employ a razor-sharp sense of smell to tip them off that a warm-blooded meal is nearby, and then use vision and other senses to home in on the feast.

“Very little was known about what a host looks like to the mosquito and how a mosquito decides where to land and begin to feed,” said UW biologist , co-author on the paper and one of three professors collaborating on these efforts.

Experiments by other scientists implied that the mosquito sense of smell might activate other senses in the quest for a host. But Riffell and his colleagues wanted to understand what those triggers are, and which sensory pathways are most critical for finding a meal. They used wind tunnels to observe mosquitoes, placing them in an enclosed environment where they could record and track their behavior.

“What’s great about this wind tunnel is that it provided a nice control of wind conditions and the environment these mosquitoes are flying around in,” said Riffell. “We can really test different cues and the mosquito’s response to them.”

The wind tunnels were mostly featureless, with the exception of a small dark dot on the floor. To test the role scent played in mosquito behavior, the researchers released a plume of carbon dioxide — the gas we exhale with each breath — into the wind tunnel and observed how mosquito behavior changed. It turned out that carbon dioxide triggered a strong response in the mosquitoes.

“When we gave them the odor stimulus, all of the sudden they were attracted to this black dot,” said Riffell. “It’s almost like the carbon dioxide gas turned on the visual stimulus for the mosquitoes to go to this black dot.”

Riffell believes the mosquitoes went to the black dot — a high-contrast spot in an otherwise featureless environment — thinking that a warm-blooded host was nearby. These results might mean that mosquitoes control or “gate” their sensory systems. They may not seek a host until they smell one — in this case, due to the scent of our exhaled breath. If this theory is correct, the scents picked up by the mosquito’s nose may determine whether or not it engages other sensory sensory systems in the search, especially vision.

Adding heat or water vapor to the black dot increased the mosquitoes’ affinity for the dot after carbon dioxide was released into the wind tunnel. Riffell and his colleagues plan to study how other scents might affect mosquito behavior.

“Carbon dioxide is the best signal for a warm-blooded animal, and they can sense that from up to 30 feet away — quite a distance,” said Riffell. “And then they start using vision and other body odors to discriminate whether we’re a dog or a deer or a cow or a human. That may be how they discriminate among potential blood hosts.”

If so, the experiments Riffell and his collaborators are doing now may prove this theory. They are recording how the nerve cells in specific regions of the mosquito brain respond to other odors, which may indicate which scents are most important for attracting mosquitoes to feed. They may also identify odors that repel mosquitoes rather than attract them.

Riffell and his colleagues hope these nerve cell recording experiments will help them understand how insects integrate and interpret different signals from their environment and use this information to make decisions. This information could someday be used to help control mosquitoes, particularly the species that spread dangerous pathogens.

“A lot of papers have been trying to find these odor sources that could repel or attract mosquitoes,” said Riffell. “What our research shows is that it’s not one kind of odor or stimulus that’s attracting mosquitoes, it’s a real combination of cues.”

The experiments in the Current Biology paper began in the UW biology department before professor , the paper’s senior author, relocated to Caltech. Riffell, Dickinson and UW physiology and biophysics professor — who is also a co-author — are continuing their collaboration at both institutions.

This research was funded by the National Institutes of Health.

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For more information, contact Riffell at 310-488-1227 or jriffell@uw.edu.

Grant number: NIHRO1DCO13693-01

The study, published online in , is among the first to identify structural white matter and functional gray matter differences in the brain between children with dyslexia and dysgraphia, and between those children and typical language learners. The researchers say the findings underscore the need to provide instruction tailored to each of these specific learning disabilities, though that is currently not mandated under federal or state law.

“This shows that there’s a brain basis for these different disabilities,” said co-author , a psychologist who heads the UW Learning Disabilities Center, funded by the National Institute of Child Health and Human Development. “So they require different diagnoses, and different instruction. We’ve got to start acknowledging this.”

The study involved 40 children in grades 4 to 9, including 17 diagnosed with dyslexia — persisting difficulty with word reading and spelling — and 14 diagnosed with dysgraphia, persisting difficulty with handwriting, along with 9 typical language learners. The children were asked to write the next letter in the alphabet following a letter they were shown, to write the missing letter in a word spelling, to rest without any task, and to plan a text about astronauts.

The children used a developed at the UW that allowed researchers to record their writing in real time while their active brain connections were measured with functional magnetic resonance imaging, or fMRI.

The three groups differed from each other in written language and cognitive tasks. The control group had more connections, which facilitate functional connections in for language processing and cognitive thinking. By contrast, children with dyslexia and dysgraphia showed less white matter connections and more functional connections to gray matter locations — in other words, their brains had to work harder to accomplish the same tasks.

“Their brains were less efficient for language processing,” said lead author , a UW professor of radiology.

The results, Berninger said, show that the two specific learning disabilities are not the same because the white matter connections and patterns and number of gray matter functional connections were not the same in the children with dyslexia and dysgraphia — on either the writing or cognitive thinking tasks.

Federal law guarantees a free and appropriate public education to children with learning disabilities, but does not require that specific types of learning disabilities are diagnosed, or that schools provide evidence-based instruction for dyslexia or dysgraphia. Consequently, the two conditions are lumped together under a general category for learning disabilities, Berninger said, and many schools do not recognize them or offer specialized instruction for either one

“There’s just this umbrella category of learning disability,” said Berninger. “That’s like saying if you’re sick you qualify to see a doctor, but without specifying what kind of illness you have, can the doctor prescribe appropriate treatment?”

“Many children struggle in school because their specific learning disabilities are not identified and they are not provided appropriate instruction,” Berninger said. Recent published in February in Computers & Education shows that computerized instruction has tremendous potential to help time-strapped teachers in regular classrooms provide such instruction for children with dyslexia and dysgraphia, but only if they are correctly diagnosed.

“Dyslexia and dysgraphia are not the only kinds of learning disabilities. One in five students in the United States may have some kind of a specific learning disability,” Berninger said. “We just can’t afford to put 20 percent of children in special education classes. There just aren’t the dollars.”

Other co-authors are , director of the UW Integrated Brain Imaging Center; , a UW senior fellow in radiology; UW research scientists Katie Askren, Paul Robinson and Kevin Yagle; UW undergraduate students Desiree Gulliford, Zoe Mestre and Olivia Welker; and William Nagy, a professor of education at Seattle Pacific University.