Allen Institute researchers decode patterns that make our brains human

Each of our human brains is special, carrying distinctive memories and giving rise to our unique thoughts and actions. Most research on the brain focuses on what makes one brain different from another. But recently, Allen Institute researchers turned the question around.

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“So much research focuses on the variations between individuals, but we turned that question on its head to ask, what makes us similar?” says Ed Lein, Ph.D., Investigator at the Allen Institute for Brain Science. “What is the conserved element among all of us that must give rise to our unique cognitive abilities and human traits?”

Their work, published this month in Nature Neuroscience, looked at gene expression across the entire human brain and identified a surprisingly small set of molecular patterns that dominate gene expression in the human brain and appear to be common to all individuals.

“Looking at the data from this unique vantage point enables us to study gene patterning that we all share,” says Mike Hawrylycz, Ph.D., Investigator at the Allen Institute for Brain Science. “We used the Allen Human Brain Atlas data to quantify how consistent the patterns of expression for various genes are across human brains, and to determine the importance of the most consistent and reproducible genes for brain function.”

Despite the anatomical complexity of the brain and the complexity of the human genome, most of the patterns of gene usage across all 20,000 genes could be characterized by just 32 expression patterns. The most highly stable genes—the genes that were most consistent across all brains—include those that are associated with diseases and disorders like autism and Alzheimer’s and include many existing drug targets. These patterns provide insights into what makes the human brain distinct and raise new opportunities to target therapeutics for treating disease.

Allen Institute researchers decode patterns that make our brains human

Conserved gene patterning across human brains provide insights into health and disease

The human brain may be the most complex piece of organized matter in the known universe, but Allen Institute researchers have begun to unravel the genetic code underlying its function. Research published this month in Nature Neuroscience identified a surprisingly small set of molecular patterns that dominate gene expression in the human brain and appear to be common to all individuals, providing key insights into the core of the genetic code that makes our brains distinctly human.

“So much research focuses on the variations between individuals, but we turned that question on its head to ask, what makes us similar?” says Ed Lein, Ph.D., Investigator at the Allen Institute for Brain Science. “What is the conserved element among all of us that must give rise to our unique cognitive abilities and human traits?”

Researchers used data from the publicly available Allen Human Brain Atlas to investigate how gene expression varies across hundreds of functionally distinct brain regions in six human brains. They began by ranking genes by the consistency of their expression patterns across individuals, and then analyzed the relationship of these genes to one another and to brain function and association with disease.

“Looking at the data from this unique vantage point enables us to study gene patterning that we all share,” says Mike Hawrylycz, Ph.D., Investigator at the Allen Institute for Brain Science. “We used the Allen Human Brain Atlas data to quantify how consistent the patterns of expression for various genes are across human brains, and to determine the importance of the most consistent and reproducible genes for brain function.”

Despite the anatomical complexity of the brain and the complexity of the human genome, most of the patterns of gene usage across all 20,000 genes could be characterized by just 32 expression patterns. While many of these patterns were similar in human and mouse, the dominant genetic model organism for biomedical research, many genes showed different patterns in human. Surprisingly, genes associated with neurons were most conserved across species, while those for the supporting glial cells showed larger differences.

The most highly stable genes—the genes that were most consistent across all brains—include those that are associated with diseases and disorders like autism and Alzheimer’s and include many existing drug targets. These patterns provide insights into what makes the human brain distinct and raise new opportunities to target therapeutics for treating disease.

The researchers also found that the pattern of gene expression in cerebral cortex is correlated with “functional connectivity” as revealed by neuroimaging data from the Human Connectome Project. “It is exciting to find a correlation between brain circuitry and gene expression by combining high quality data from these two large-scale projects,” says David Van Essen, Ph.D., professor at Washington University in St. Louis and a leader of the Human Connectome Project.

“The human brain is phenomenally complex, so it is quite surprising that a small number of patterns can explain most of the gene variability across the brain,” says Christof Koch, Ph.D., President and Chief Scientific Officer at the Allen Institute for Brain Science. “There could easily have been thousands of patterns, or none at all. This gives us an exciting way to look further at the functional activity that underlies the uniquely human brain.”

This research was conducted in collaboration with the Cincinnati Children’s Hospital and Medical Center and Washington University in St. Louis.

The project described was supported by award numbers 1R21DA027644 and 5R33DA027644 from the National Institute on Drug Abuse. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health and the National Institute on Drug Abuse.

About the Allen Institute for Brain Science

The Allen Institute for Brain Science is an independent, 501(c)(3) nonprofit medical research organization dedicated to accelerating the understanding of how the human brain works in health and disease. Using a big science approach, the Allen Institute generates useful public resources used by researchers and organizations around the globe, drives technological and analytical advances, and discovers fundamental brain properties through integration of experiments, modeling and theory. Launched in 2003 with a seed contribution from founder and philanthropist Paul G. Allen, the Allen Institute is supported by a diversity of government, foundation and private funds to enable its projects. Given the Institute’s achievements, Mr. Allen committed an additional $300 million in 2012 for the first four years of a ten-year plan to further propel and expand the Institute’s scientific programs, bringing his total commitment to date to $500 million. The Allen Institute’s data and tools are publicly available online at brain-map.org.

ORIGINAL: Allen Institute

November 16, 2015

Scientists insert happy memories into the brains of sleeping mice

Image: Shutterstock/rkucharek

It was all a dream - or was it? Scientists have successfully hacked into the brains of napping mice, implanting false but cheerful memories via electrode stimulation, and demonstrating for the first time that memory manipulation during sleep is possible.

The team from the National Centre for Scientific Research (CRNS) in France managed to create positive feelings about a specific location that five mice had explored earlier in the day. They did this by stimulating their brains as they slept. So strong were these feelings, that when the mice woke up, they immediately wandered back to that location, presumably seeking some kind of reward.

“The mouse develops a goal-directed behaviour to go towards the place,” lead author Karim Benchenane told NewScientist. “It proves that it's not an automatic behaviour. What we create is an association between a particular place and a reward that can be consciously accessed by the mouse.”

The results of the study have been published in Nature Neuroscience.

The idea of memory manipulation is totally reminiscent of Michel Gondry's film Eternal Sunshine of the Spotless Mind, where the protagonist and his former love interest both have the painful memories of their relationship wiped clean. Predictably, when certain things (objects, songs, letters, etc.) trigger old, no-longer-existent memories, a bit of confusion ensues.

It’s an interesting, if somewhat troubling premise, but in future, with more testing and less invasive procedures, it’s exactly where memory manipulation technologies like this one could find applications.

“The idea is to use this as a tool for post-traumatic stress disorder,” Benchenane told Hannah Devlin from The Guardian.

“I think this is a really important step towards helping people with memory impairments or depression,” Loren Frank, a neuroscientist from the University of California, San Francisco who wasn't involved in the study, told Jessica Hamzelou from NewScientist. “In principle, you could selectively change brain processing during sleep to soften memories or change their emotional content.”

The researchers wanted to test the hypothesis that mice, like humans, consolidate memories as they sleep, replaying the day's events and learning in the process.

In order to insert their false memories, the researchers needed to first locate specific neurons, or place cells, within the mice’s brains that fire signals and help form spatial memories about specific locations.

The researchers implanted electrodes into the hippocampus - the region of the brain associated with memory formation - of five mice. The electrodes recorded neural activity while the mice explored a new environment, and the researchers were able to identify spikes in activity associated with specific locations.

Each mouse was then monitored during a one-hour nap. When place cells began firing it suggested to researchers that the mouse was recalling its experience from earlier in the day. Each time these cells fired, the researchers used a separate electrode to stimulate a region of the brain associated with pleasure.

As Hamzelou from NewScientist reports: “When the mice awoke, they made a beeline for the location represented by the place cell that had been linked to a rewarding feeling in their sleep. A brand new memory - linking a place with reward - had been formed."

Neuroscientist Neil Burgess at University College London, who wasn’t involved in the research, told NewScientist it was a "bigger breakthrough" than previous studies, adding: “The mouse is remembering enough abstract information to think ‘I want to go to a certain place', and go there when it wakes up.”

The researchers say one of the next steps is to see if the same results can be achieved during rapid eye movement sleep - a stage of sleep the mice didn't enter during their short one-hour siesta.

MYLES GOUGH 9 MAR 2015

Other teams are also bringing us closer to the realisation of memory manipulation. In August 2014, scientists in the US used lasers to flip negative memories into happy ones in mice, and DARPA has an ambitious program to restore memories in veterans who have suffered traumatic brain injuries.

Sources: NewScientist, The Guardian


ORIGINAL: Science Alert

MYLES GOUGH 

 9 MAR 2015

A Brain-Computer Interface That Works Wirelessly

A wireless transmitter could give paralyzed people a practical way to control TVs, computers, or wheelchairs with their thoughts.

Why It Matters

Electronic brain interfaces may give paralyzed people control over their environments. 

A wireless brain interface uses the head-worn transmitter, shown.

A few paralyzed patients could soon be using a wireless brain-computer interface able to stream their thought commands as quickly as a home Internet connection.

After more than a decade of engineering work, researchers at Brown University and a Utah company, Blackrock Microsystems, have commercialized a wireless device that can be attached to a person’s skull and transmit via radio thought commands collected from a brain implant. Blackrock says it will seek clearance for the system from the U.S. Food and Drug Administration, so that the mental remote control can be tested in volunteers, possibly as soon as this year.

The device was developed by a consortium, called BrainGate, which is based at Brown and was among the first to place implants in the brains of paralyzed people and show that electrical signals emitted by neurons inside the cortex could be recorded, then used to steer a wheelchair or direct a robotic arm (see “Implanting Hope”).

A major limit to these provocative experiments has been that patients can only use the prosthetic with the help of a crew of laboratory assistants. The brain signals are collected through a cable screwed into a port on their skull, then fed along wires to a bulky rack of signal processors. “Using this in the home setting is inconceivable or impractical when you are tethered to a bunch of electronics,” says Arto Nurmikko, the Brown professor of engineering who led the design and fabrication of the wireless system.

The new interface does away with much of that wiring by processing brain data inside a device about the size of an automobile gas cap. It is attached to the skull and wired to electrodes inside the brain. Inside the device is 

• a processor to amplify the faint electrical spikes emitted by neurons, 
• circuits to digitize the information, and 
• a radio to beam it a distance of a few meters to a receiver. 

There, the information is available as a control signal; say to move a cursor across a computer screen.
The device transmits data out of the brain at rate of 48 megabits per second, about as fast as a residential Internet connection, says Nurmikko. It uses about 30 milliwatts of power—a fraction of what a smartphone uses—and is powered by a battery.

Scientists have prototyped wireless brain-computer interfaces before, and some simpler transmitters have been sold for animal research. “But there’s just no such thing as a device that has this many inputs and spits out megabits and megabits of data. It’s fundamentally a new kind of device,” says Cindy Shestek, an assistant professor of biomedical engineering at the University of Michigan.

Although the implant can transmit the equivalent of about 200 DVDs’ worth of data a day, that’s not much information compared to what the brain generates in executing even the simplest movement. Of the billions of neurons in the human cortex, scientists have never directly measured more than 200 or so simultaneously. “You and I are using our brains as petabyte machines,” says Nurmikko. “By that standard, 100 megabits per second is going to look very modest.”

Blackrock has begun selling the wireless processor, which it calls “Cereplex-W” and costs about $15,000, to research labs that study primates. Tests in humans could happen quickly, says Florian Solzbacher, a University of Utah professor who is the owner and president of Blackrock. The Brown scientists have plans to try it on paralyzed patients, but haven’t yet done so.

Currently, a half dozen or so paralyzed people, including some in the late stages of ALS, are taking part in BrainGate trials using the older technology. In those studies, underway in Boston and California, the implant that makes contact with the brain is a small array of needle-like electrodes carved from silicon. Also sold by Blackrock, it is commonly called the Utah array. To establish a brain-machine interface, that array is pushed into the tissue of the cerebral motor cortex, where its tips record the firing patterns from 100 neurons or more at once.

Those tiny blasts of electricity, scientists have found, can be decoded into a fairly precise readout of what movement an animal, or a person, is intending. Decoding those signals has permitted hundreds of monkeys, as well as a growing number of paralyzed volunteers, to control a computer mouse, or manipulate objects with a robotic arm, sometimes with surprising dexterity (see “The Thought Experiment”).


But the BrainGate technology will never turn into actual medicine until it’s greatly simplified and made more reliable. The head-mounted wireless module is a step toward that goal. Eventually, scientists say, all the electronics will have to be implanted completely inside the body, with no wires reaching through the skin, since that can lead to infections. Last year, the Brown researchers reported testing a prototype of a fully implanted interface, with the electronics housed inside a titanium can that can be sealed under the scalp. That device is not yet commercialized.

“If they could put it in under the skin, then everything you see in the videos could be done at home,” says Shestek, referring to films of patients using mental control to move robotic arms. “That wire going through the skin is the most dangerous part of the system.”

ORIGINAL: Tech Review

By Antonio Regalado 

January 14, 2015