The backwards brain? How brain maps develop to help us perceive the world

 

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Artist's abstraction (stock illustration).

Driving to work becomes routine -- but could you drive the entire way in reverse gear? Humans, like many animals, are accustomed to seeing objects pass behind us as we go forward. Moving backwards feels unnatural.

In a new study, scientists from The Scripps Research Institute (TSRI) reveal that moving forward actually trains the brain to perceive the world normally. The findings also show that the relationship between neurons in the eye and the brain is more complicated than previously thought -- in fact, the order in which we see things could help the brain calibrate how we perceive time, as well as the objects around us.

"We were trying to understand how that happens and the rules used during brain development," said the study's senior author Hollis Cline, who is the Hahn Professor of Neuroscience and member of the Dorris Neuroscience Center at TSRI.

This research, published this week in the journal Proceedings of the National Academy of Sciences could have implications for treating sensory processing disorders such as autism.

Reversing the Map

The new study began when Masaki Hiramoto, a staff scientist in Cline's lab, asked an important question: "How does the visual system of the brain get better "tuned" over time?"

Previous studies had shown that people use the visual system to create an internal map of the world. The key to creating this map is sensing the "optic flow" of objects as we walk or drive forward. "It's natural because we've learned it," said Cline.

To study how this system develops, Hiramoto and Cline used transparent tadpoles to watch as nerve fibers, called axons, developed between the retina and the brain. The scientists marked the positions of the axons using fluorescent proteins.

The tadpoles were split into groups and raised in small chambers. One group was shown a computer screen with bars of light that moved past the tadpoles from front to back -- simulating a normal optic flow as if the animal were moving forward. A second group saw the bars in reverse -- simulating an unnatural backwards motion. Using the TSRI Dorris Neuroscience Center microscopy facility, Hiramoto then captured high-resolution images of these neurons as they grew over time.

The researchers found that tadpoles' visual map developed normally when shown bars moving from front to back. But tadpoles shown the bars in reverse order extended axons to the wrong spots in their map. With those axons out of order, the brain would perceive visual images as reversed or squished.

Rewriting the Rules

This discovery challenges a rule in neuroscience that dates back to 1949. Until now, researchers knew it was important that neighboring neurons fired at roughly the same time, but didn't realize that the temporal sequence of firing was important.

"According to the old rule, if there was a stimulus that went backwards, the map would be fine," said Cline.

The new study adds the element of order. The researchers showed that objects moving from front to back in the visual field activated retinal cells in a specific sequence.

Cline and Hiramoto believe that this sequence helps the brain perceive the passage of time. For example, if you drive for a few minutes and pass a street sign, your brain will map its position behind you. If you keep driving and you pass another street sign, your brain will map out not only the street signs' positions relative to each other, but their distance in time as well.

This link between time and space in the visual system might also apply to hearing and the sense of touch. The original question of how the visual system gets "tuned" over time might be applicable across the entire brain.

The researchers believe this study could have implications for patients with sensory and temporal processing disorders, including autism and a mysterious disorder called Alice in Wonderland syndrome, where a person perceives objects as disproportionately big or small. Cline said the new study offers possibilities for retraining the brain to map the world correctly, for instance after stroke.

Support for the work came from the National Institutes of Health (EY011261 and DP1OD000458), the Nancy Lurie Marks Family Foundation and an endowment from the Hahn Family Foundation.

Scientists Discovered a Part of Brain that Motivates Us to Exercise

 

Posted By Recail On Friday, September 26, 2014 11:26 PM. Under Fitness Tips, Health Tips

In recent years, there have been many studies about the relationship between your neural messages and motivation for exercise. Scientists have believed that there must be a reason why some people are motivated to exercise, while others don’t feel the need. The claims made by the scientists have finally seen some positive backing.

According to a recent study, scientists discovered that a tiny region in the human brain is responsible for controlling a person’s desire to sprint and participate in some other rewarding activities. The study was conducted on mice, and noted their motivation for running.

The region of brain responsible for this motivation is called Dorsal Medial Habenula. The structure in mice is similar to the region in men. Scientists believe that this region’s ability to regulate motivation and mood should be similar across the two different species.

According to Head Researcher, Seattle Children’s Research Institute, Eric Turner, some significant changes in the physical activity and a person’s inability to enjoy pleasurable or rewarding experiences are two major causes of depression. 

He believes that the brain pathways that play an important role for exercise motivation aren’t well understood. With some new and effective ways to manipulate activity within particular brain areas, researchers plan to develop more effective and targeted treatments for depression. Researchers are positive about developing some effective ways to accomplish these goals without having any impact on the rest of brain activity.

During their research, Eric Turner and other researchers focused on genetically engineered mice. They tried to block various signals from the mice’s Dorsal Medial Habenula. As compared to regular mice who always love to sprint on wheels, genetically engineered mice ran less, and even felt lethargic. As a side note, this is not the first time in the recent past that we explored depression with the aid of mice. A study conducted in 2006 used mice to test the hypothesis that the deficiency of certain proteins, particularly p11, can also lead to depression. The researchers concluded that if the lacking protein was introduced in form of supplements, the mood of the animals significantly improved.

Recently, Turner explained in a press release that the lack of a functioning Dorsal Medial Habenula, the genetically engineered mice acted like couch potatoes. Although these mice were capable of running, they didn’t have the motivation to sprint on wheels.

Eric Turner also explained that these genetically engineered mice didn’t prefer sweetened, delicious drinking water instead of regular water. It’s important to understand that the lack of basic exercise and desire to seek pleasure led to depression in the mice. These mice didn’t care anymore about their health and well being.

The research team also conducted another experiment. In this experiment, researches precisely targeted light to the Dorsal Medial Habenula of the mice. When the mice turned one of the two wheels using their paws, they were able to voluntarily activate the specific region in the brain.

Could Deep-Brain Stimulation Fortify Soldiers’ Minds?

 

By S. Matthew Liao | September 4, 2014

The views expressed are those of the author and are not necessarily those of Scientific American.

 

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As many as 20 percent of war veterans return from combat in Afghanistan and Iraq with post-traumatic stress disorder (PTSD) or major depression, according to a 2008 report from the RAND Corporation. Many experience constant nightmares and flashbacks and many can’t live normal lives. For significant number of veterans, available medications do not seem to help. In 2010, at least 22 veterans committed suicide each day, according to the Department of Veterans Affairs. In her book, Demon Camp, the author Jen Percy describes damaged veterans who have even resorted to exorcism to alleviate their PTSD symptoms.

U.S. Army Soldiers with the 4th Brigade, 1st Infantry Division stand guard at a market in Al Doura in Baghdad, Iraq, April 5, 2007, providing security for Ryan Crocker, U.S. ambassador to Iraq. (U.S. Army photo by Sgt. Curt Cashour via Flickr)

As part of President Obama’s BRAIN Initiative, the federal Defense Advanced Research Projects Agency (DARPA) plans to spend more than $70 million over five years to develop novel devices that would address neurological disorders such as PTSD. DARPA is particularly interested in a technology called Deep Brain Stimulation (DBS). DBS involves inserting a thin electrode through a small opening in the skull into a specific area in the brain; the electrode is then connected by an insulated wire to a battery pack underneath the skin; the battery pack then sends electrical pulses via the wire to the brain.

About 100,000 people around the world today have a DBS implant to ameliorate the effects of Parkinson’s disease, epilepsy and major depression. There is evidence that DBS can also help with PTSD. Functional neuroimaging studies indicate that amygdala hyperactivity is responsible for the symptoms of PTSD and that DBS can functionally reduce the activity of the amygdala. In animal PTSD models, DBS has been found to be more effective than current treatment using selective serotonin reuptake inhibitors.

DARPA’s SUBNETS program seeks new neurotechnology for analyzing neuronal activity across sub-networks of the brain to enable next-generation therapies tailored to individual patients. (DARPA image)

DARPA wants to develop the next-generation, deep brain stimulators (call them DBS+) that do not require user input and that can a) read and monitor the brain’s activities in real-time using neural recording, and b) intervene in these activities in an automatic way through electrical stimulation.

DARPA’s officially stated goal is to treat soldiers who have PTSD and other related neurological disorders. However, once DBS+ is developed, theoretically it could also be used to fortify soldiers’ minds. For example, DBS+ could be used to pre-empt PTSD. Suppose that a soldier has just experienced a potentially traumatic event. DBS+ could be used to detect and categorize the emotional reaction in the amygdala. Like tsunami warnings, there could be different categories. If DBS+ detected a Category 4 reaction, it would automatically reduce the activity in the amygdala to a certain degree. If DBS+ detected a Category 5 reaction, it would slow the amygdala to a halt.

When the emotional strength of one’s memory is reduced, the memory tends not to get consolidated as strongly into long-term memory. Indeed, in both military and non-military settings, the beta-blocker propranolol has been used to dampen the emotional strength of one’s memory as a means of reducing potential trauma. By monitoring the brain in real time and intervening when necessary, DBS+ has the potential to be more precise and efficient while having fewer side effects.

The research team led by Massachusetts General Hospital will use a combination of commercial-off-the-shelf electrodes and custom technology developed by Draper Labs to create novel systems. The proposed design will focus on an ultra-low-profile, hermetically sealed interface device capable of being recharged through inductive coupling. (DARPA image courtesy of Massachusetts General Hospital and Draper Labs)

Once DBS+ is developed, it could also be used to modulate other emotions. Suppose that a soldier is about to enter combat. DBS+ could be used to reduce/remove fear and/or increase courage by increasing adrenaline in the soldier, much like psychotropic drugs such as amphetamine that some soldiers now use. In animal models, DBS reduces fear expressions when applied to the dorsal area of the ventral striatum.

The development of DBS+ will raise familiar but important questions that pertain to the development of all new biotechnologies, including safety and risks. Also, DBS+ is likely to raise some of the same ethical issues that current DBS faces, such as those of authenticity and alienation. For instance, after using DBS, some patients have said things like “During those years of illness, I was asleep. But now I’m going to take my life back.” Others have said things like “I don’t recognize myself anymore.”

The benefits of DBS+ will therefore need to be weighed against its damaging potential to distort or disturb our sense of self. Moreover, DBS has been known to have unintended negative and positive effects. In some patients with Parkinson’s disease, DBS has taken away their tremors but also their passion to lead an active life. In other patients with Parkinson’s disease, DBS has made these patients feel ‘well’ and ‘happy’ even though DBS has not reduced their symptoms. These issues will make DBS+ a future technology that is likely to generate serious public debates.

But even if DBS+ is safe, some people will rightly be concerned that soldiers may be forced to use this kind of brain modification. Suppose soldiers were only equipped with DBS+ on condition of their informed consent after being properly informed of the various risks and benefits. Would all the ethical concerns have been addressed? Perhaps not.

Even if there were informed consent, there could be subtler forms of coercion. The military command structure is hierarchical. This could make “consent” less than fully voluntary. If a commanding officer were to strongly urge the use of DBS+, would this not influence the choices of subordinate officers? Also, there may be subtle or not-so-subtle forms of peer pressure. A soldier may agree to use DBS+ because the soldier does not want to let fellow soldiers down. Moreover, if a soldier does not use DBS+, the soldier may be at a competitive disadvantage. Soldiers with DBS+ may be more reliable under pressure than soldiers without DBS+ and may therefore be more likely to be called upon and shouldered with responsibility.

Could we just ban the use of DBS+ in the military, just as we ban the use of steroids in sports? It is not clear that this is a viable option. Soldiers are already enhanced in other ways. They have access to night vision goggles, Apache helicopters and drugs such as Modafinil to improve alertness and Ritalin to enhance attention. Also, banning doping in sports is usually done for considerations of fairness, but these reasons are unlikely to sway any soldier/state institutions. Would any soldier voluntarily give up advanced military weaponry just to level the playing field? Moreover, if one’s enemies have acquired the technology and are using it, this will undoubtedly provide a strong incentive for its use.

Others might worry that using DBS+ would lead to conscienceless soldiers who would kill indiscriminately in ways that are out of reasonable proportion. This is a serious and important concern. Interestingly, this may be a “technical” problem.

Brain implants that reduce or eliminate our sense of morality are morally undesirable and are not really enhancements as such. Efforts should therefore be made to ensure that the kind of brain implants we develop do not have these unwanted side effects. In the short term, the brain implants we develop may well be imperfect in just such a way. If so, this would be a good reason to ban such devices in the short term. The interesting theoretical issue is what happens when we have perfected the technology and have brain implants that would enable a soldier to kill at the right time, for the right reasons, and in a proportionate manner? Would we still have ethical problems with soldiers using such a technology?

DARPA taps Lawrence Livermore to develop world's first neural device to restore memory

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Lawrence Livermore National Laboratory (LLNL) will develop an implantable neural device with the ability to record and stimulate neurons within the brain to help restore memory.

The Department of Defense's Defense Advanced Research Projects Agency (DARPA) awarded Lawrence Livermore National Laboratory (LLNL) up to $2.5 million to develop an implantable neural device with the ability to record and stimulate neurons within the brain to help restore memory, DARPA officials announced this week.

The research builds on the understanding that memory is a process in which neurons in certain regions of the brain encode information, store it and retrieve it. Certain types of illnesses and injuries, including Traumatic Brain Injury (TBI), Alzheimer's disease and epilepsy, disrupt this process and cause memory loss. TBI, in particular, has affected 270,000 military service members since 2000.

The goal of LLNL's work -- driven by LLNL's Neural Technology group and undertaken in collaboration with the University of California, Los Angeles (UCLA) and Medtronic -- is to develop a device that uses real-time recording and closed-loop stimulation of neural tissues to bridge gaps in the injured brain and restore individuals' ability to form new memories and access previously formed ones.

The research is funded by DARPA's Restoring Active Memory (RAM) program.

Specifically, the Neural Technology group will seek to develop a neuromodulation system -- a sophisticated electronics system to modulate neurons -- that will investigate areas of the brain associated with memory to understand how new memories are formed. The device will be developed at LLNL's Center for Bioengineering.

"Currently, there is no effective treatment for memory loss resulting from conditions like TBI," said LLNL's project leader Satinderpall Pannu, director of the LLNL's Center for Bioengineering, a unique facility dedicated to fabricating biocompatible neural interfaces. "This is a tremendous opportunity from DARPA to leverage Lawrence Livermore's advanced capabilities to develop cutting-edge medical devices that will change the health care landscape."

LLNL will develop a miniature, wireless and chronically implantable neural device that will incorporate both single neuron and local field potential recordings into a closed-loop system to implant into TBI patients' brains. The device -- implanted into the entorhinal cortex and hippocampus -- will allow for stimulation and recording from 64 channels located on a pair of high-density electrode arrays. The entorhinal cortex and hippocampus are regions of the brain associated with memory.

The arrays will connect to an implantable electronics package capable of wireless data and power telemetry. An external electronic system worn around the ear will store digital information associated with memory storage and retrieval and provide power telemetry to the implantable package using a custom RF-coil system.

Designed to last throughout the duration of treatment, the device's electrodes will be integrated with electronics using advanced LLNL integration and 3D packaging technologies. The microelectrodes that are the heart of this device are embedded in a biocompatible, flexible polymer.

Using the Center for Bioengineering's capabilities, Pannu and his team of engineers have achieved 25 patents and many publications during the last decade. The team's goal is to build the new prototype device for clinical testing by 2017.

Lawrence Livermore's collaborators, UCLA and Medtronic, will focus on conducting clinical trials and fabricating parts and components, respectively.

"The RAM program poses a formidable challenge reaching across multiple disciplines from basic brain research to medicine, computing and engineering," said Itzhak Fried, lead investigator for the UCLA on this project andprofessor of neurosurgery and psychiatry and biobehavioral sciences at the David Geffen School of Medicine at UCLA and the Semel Institute for Neuroscience and Human Behavior. "But at the end of the day, it is the suffering individual, whether an injured member of the armed forces or a patient with Alzheimer's disease, who is at the center of our thoughts and efforts."

LLNL's work on the Restoring Active Memory program supports President Obama's Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative.

"Our years of experience developing implantable microdevices, through projects funded by the Department of Energy (DOE), prepared us to respond to DARPA's challenge," said Lawrence Livermore Engineer Kedar Shah, a project leader in the Neural Technology group.

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Story Source:

The above story is based on materials provided by DOE/Lawrence Livermore National Laboratory. Note: Materials may be edited for content and length.

The less older adults sleep, the faster their brains age, new study suggests

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Researchers at Duke-NUS Graduate Medical School Singapore (Duke-NUS) have found evidence that the less older adults sleep, the faster their brains age. These findings, relevant in the context of Singapore's rapidly ageing society, pave the way for future work on sleep loss and its contribution to cognitive decline, including dementia.

Past research has examined the impact of sleep duration on cognitive functions in older adults. Though faster brain ventricle enlargement is a marker for cognitive decline and the development of neurodegenerative diseases such as Alzheimer's, the effects of sleep on this marker have never been measured.

The Duke-NUS study examined the data of 66 older Chinese adults, from the Singapore-Longitudinal Aging Brain Study(1). Participants underwent structural MRI brain scans measuring brain volume and neuropsychological assessments testing cognitive function every two years. Additionally, their sleep duration was recorded through a questionnaire. Those who slept fewer hours showed evidence of faster ventricle enlargement and decline in cognitive performance.

"Our findings relate short sleep to a marker of brain aging," said Dr June Lo, the lead author and a Duke-NUS Research Fellow. "Work done elsewhere suggests that seven hours a day(2) for adults seems to be the sweet spot for optimal performance on computer based cognitive tests. In coming years we hope to determine what's good for cardio-metabolic and long term brain health too," added Professor Michael Chee, senior author and Director of the Centre for Cognitive Neuroscience at Duke-NUS.

Notes:

1) The Singapore-Longitudinal Aging Brain Study (started in 2005) follows a cohort of healthy adults of Chinese ethnicity aged 55 years and above. This study is one of the few in Asia that tracks the brain structures and cognitive functions of older adults so closely.

2) Data collected by Lumosity, an online brain-training program, suggests that self-reported sleep duration of seven hours is associated with the best cognitive test scores in over 150,000 adults. As of now it is unknown if this amount of sleep is optimum for cardio metabolic and long-term brain health.

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Story Source:

The above story is based on materials provided by Duke-NUS Graduate Medical School Singapore. Note: Materials may be edited for content and length.

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Journal Reference:

1. June C. Lo, Kep Kee Loh, Hui Zheng, Sam K.Y. Sim, Michael W.L. Chee. Sleep Duration and Age-Related Changes in Brain Structure and Cognitive Performance. SLEEP, 2014; DOI: 10.5665/sleep.3832

Early life stress can leave lasting impacts on the brain

 

June 27, 2014

University of Wisconsin-Madison

For children, stress can go a long way. A little bit provides a platform for learning, adapting and coping. But a lot of it — chronic, toxic stress like poverty, neglect and physical abuse — can have lasting negative impacts. A team of researchers recently showed these kinds of stressors, experienced in early life, might be changing the parts of developing children’s brains responsible for learning, memory and the processing of stress and emotion.

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Different forms of early life stress, such as child maltreatment or poverty, impacted the size of two important brain regions: the hippocampus (shown in red) and amygdala (shown in green), according to new University of Wisconsin-Madison research. Children who experienced such stress had small amygdalae and hippocampai, which was related to behavioral problems in these same individuals.

For children, stress can go a long way. A little bit provides a platform for learning, adapting and coping. But a lot of it — chronic, toxic stress like poverty, neglect and physical abuse — can have lasting negative impacts.

A team of University of Wisconsin-Madison researchers recently showed these kinds of stressors, experienced in early life, might be changing the parts of developing children’s brains responsible for learning, memory and the processing of stress and emotion. These changes may be tied to negative impacts on behavior, health, employment and even the choice of romantic partners later in life.

The study, published in the journal Biological Psychiatry, could be important for public policy leaders, economists and epidemiologists, among others, says study lead author and recent UW Ph.D. graduate Jamie Hanson.

“We haven’t really understood why things that happen when you’re 2, 3, 4 years old stay with you and have a lasting impact,” says Seth Pollak, co-leader of the study and UW-Madison professor of psychology.

Yet, early life stress has been tied before to depression, anxiety, heart disease, cancer, and a lack of educational and employment success, says Pollak, who is also director of the UW Waisman Center’s Child Emotion Research Laboratory.

“Given how costly these early stressful experiences are for society … unless we understand what part of the brain is affected, we won’t be able to tailor something to do about it,” he says.

For the study, the team recruited 128 children around age 12 who had experienced either physical abuse, neglect early in life or came from low socioeconomic status households.

Researchers conducted extensive interviews with the children and their caregivers, documenting behavioral problems and their cumulative life stress. They also took images of the children’s brains, focusing on the hippocampus and amygdala, which are involved in emotion and stress processing. They were compared to similar children from middle-class households who had not been maltreated.

Hanson and the team outlined by hand each child’s hippocampus and amygdala and calculated their volumes. Both structures are very small, especially in children (the word amygdala is Greek for almond, reflecting its size and shape in adults), and Hanson and Pollak say the automated software measurements from other studies may be prone to error.

Indeed, their hand measurements found that children who experienced any of the three types of early life stress had smaller amygdalas than children who had not. Children from low socioeconomic status households and children who had been physically abused also had smaller hippocampal volumes. Putting the same images through automated software showed no effects.

Behavioral problems and increased cumulative life stress were also linked to smaller hippocampus and amygdala volumes.

Why early life stress may lead to smaller brain structures is unknown, says Hanson, now a postdoctoral researcher at Duke University’s Laboratory for NeuroGenetics, but a smaller hippocampus is a demonstrated risk factor for negative outcomes. The amygdala is much less understood and future work will focus on the significance of these volume changes.

“For me, it’s an important reminder that as a society we need to attend to the types of experiences children are having,” Pollak says. “We are shaping the people these individuals will become.”

But the findings, Hanson and Pollak say, are just markers for neurobiological change; a display of the robustness of the human brain, the flexibility of human biology. They aren’t a crystal ball to be used to see the future.

“Just because it’s in the brain doesn’t mean it’s destiny,” says Hanson.

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Story Source:

The above story is based on materials provided by University of Wisconsin-Madison. The original article was written by Kelly April Tyrrell. Note: Materials may be edited for content and length.

Brain power: New insight into how brain regulates its blood flow

 

June 12, 2014

Columbia University School of Engineering and Applied Science

Engineering professors have identified a new component of the biological mechanism that controls blood flow in the brain, demonstrating that the vascular endothelium plays a critical role in the regulation of blood flow in response to stimulation in the living brain. Understanding how and why the brain regulates its blood flow could provide important clues to understanding early brain development, disease, and aging.

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The vasculature of the brain's cortex is organized with large arteries and veins on its surface. Arterioles dive into the cortex to feed capillary beds weaving amongst active brain cells. Ascending venules bring blood from the capillary beds to draining veins. During functional stimulation, blood flow increases in the capillary bed (hyperemia) and dilation of feeding arterioles spreads back up the vascular tree to surface arteries.

In a new study published online in the Journal of the American Heart Association June 12, 2014, researchers at Columbia Engineering report that they have identified a new component of the biological mechanism that controls blood flow in the brain. Led by Elizabeth M. C. Hillman, associate professor of biomedical engineering, the team has demonstrated, for the first time, that the vascular endothelium plays a critical role in the regulation of blood flow in response to stimulation in the living brain.

"We think we've found a missing link in our understanding of how the brain dynamically tunes its blood flow to stay in sync with the activity of neurons," says Hillman, who has a joint appointment in Radiology. Hillman has spent more than 10 years using advanced imaging tools to study how blood flow is controlled in the brain. "Earlier studies identified small pieces of the puzzle, but we didn't believe they formed a cohesive 'big picture' that unified everybody's observations. Our new finding seems to really connect the dots."

Understanding how and why the brain regulates its blood flow could provide important clues to understanding early brain development, disease, and aging. The brain increases local blood flow when neurons fire, and this increase is what is detected by a functional magnetic resonance imaging (fMRI) scan. Hillman found that the vascular endothelium, the inner layer of blood vessels, plays a critical role in propagating and shaping the blood flow response to local neuronal activity. While the vascular endothelium is known to do this in other areas of the body, until now the brain was thought to use a different, more specialized mechanism and researchers in the field were focused on the cells surrounding the vessels in the brain.

"Once we realized the importance of endothelial signaling in the regulation of blood flow in the brain," Hillman adds, "we wondered whether overlooking the vascular endothelium might have led researchers to misinterpret their results."

"As we identified this pathway, so many things fell into place," she continues, "We really hope that our work will encourage others to take a closer look at the vascular endothelium in the brain. So far, we think that our findings have far-reaching and really exciting implications for neuroscience, neurology, cardiovascular medicine, radiology, and our overall understanding of how the brain works."

This research was carried out in Hillman's Laboratory for Functional Optical Imaging, led by PhD student and lead author on the study, Brenda Chen. Other lab members who assisted with the study included PhD and MD/PhD students from Columbia Engineering, Neurobiology and Behavior, and Columbia University Medical Center. The group combined their engineering skills with their expertise in neuroscience, biology, and medicine to understand this new aspect of brain physiology.

To tease apart the role of endothelial signaling in the living brain, they had to develop new ways to both image the brain at very high speeds, and also to selectively alter the ability of endothelial cells to propagate signals within intact vessels. The team achieved this through a range of techniques that use light and optics, including imaging using a high-speed camera with synchronized, strobed LED illumination to capture changes in the color, and thus the oxygenation level of flowing blood. Focused laser light was used in combination with a fluorescent dye within the bloodstream to cause oxidative damage to the inner endothelial layer of blood brain arterioles, while leaving the rest of the vessel intact and responsive. The team showed that, after damaging a small section of a vessel using their laser, the vessel no longer dilated beyond the damaged point. When the endothelium of a larger number of vessels was targeted in the same way, the overall blood flow response of the brain to stimulation was significantly decreased.

"Our finding unifies what is known about blood flow regulation in the rest of the body with how it is regulated in the brain," Hillman explains. "This has wider reaching implications since there are many disease states known to affect blood flow regulation in the rest of the body that, until now, were not expected to directly affect brain health." For instance, involvement of the endothelium might explain neural deficits in diabetics; a clue that could lead to new diagnostics tests and treatments for neurological conditions associated with broader cardiovascular problems. "Improving our fundamental understanding of how and why the brain regulates its blood flow is key to understanding how and when this mechanism could be altered or broken," she says. "We think this could extend to studies of early brain development, aging, and diseases such as Alzheimer's and dementia."

The team's research findings may also explain the effects of some drugs on the brain, and on the fMRI response to stimulation, since the vascular endothelium is exposed to chemicals in the bloodstream. "Overall, this work could dramatically improve our ability to interpret fMRI data collected in humans, perhaps making it a better tool for doctors to understand brain disease," she adds.

Hillman plans next to address the broad range of implications her latest finding may have. She wants to explore the effects of drugs and disease states on the coupling of blood flow to neuronal activity in the brain, and is now starting studies to explore fMRI data from a range of different disease states to see whether she can find signs of neurovascular dysfunction. She is also working on characterizing the co-evolution of neuronal and hemodynamic activity during brain development and is beginning to develop new imaging tools that will enable non-invasive, inexpensive monitoring of brain hemodynamics in infants and children who cannot be imaged within an MRI scanner.

"Our latest finding gives us a new way of thinking about brain disease -- that some conditions assumed to be caused by faulty neurons could actually be problems with faulty blood vessels," Hillman adds. "This gives us a new target to focus on to explore treatments for a wide range of disorders that have, until now, been thought of as impossible to treat. The brain's vasculature is a critical partner in normal brain function. We hope that we are slowly getting closer to untangling some of the mysteries of the human brain."

This research is supported by the National Institutes of Health (through the National Institute of Neurological Disorders and Stroke) as well as the National Science Foundation, the Human Frontier Science Program and the Rodriguez family.

Brain Mapping

 

A new map, a decade in the works, shows structures of the brain in far greater detail than ever before, providing neuroscientists with a guide to its immense complexity.

Breakthrough

A high-resolution map that shows structures of the human brain as small as 20 micrometers.

Why It Matters

As neuroscientists try to understand how the brain works, they need a detailed map of its anatomy.

Key Players

• Katrin Amunts, Jülich Research Centre
• Alan Evans, Montreal Neurological Institute
• Karl Deisseroth, Stanford University

Neuroscientists have made remarkable progress in recent years toward understanding how the brain works. And in coming years, Europe’s Human Brain Project will attempt to create a computational simulation of the human brain, while the U.S. BRAIN Initiative will try to create a wide-ranging picture of brain activity. These ambitious projects will greatly benefit from a new resource: detailed and comprehensive maps of the brain’s structure and its different regions.

A section of the human brain map created by a team of international researchers shows details as small as 20 micrometers.

As part of the Human Brain Project, an international team of researchers led by German and Canadian scientists has produced a three-dimensional atlas of the brain that has 50 times the resolution of previous such maps. The atlas, which took a decade to complete, required slicing a brain into thousands of thin sections and digitally stitching them back together with the help of supercomputers. Able to show details as small as 20 micrometers, roughly the size of many human cells, it is a major step forward in understanding the brain’s three-dimensional anatomy.

To guide the brain’s digital reconstruction, researchers led by Katrin Amunts at the Jülich Research Centre in Germany initially used an MRI machine to image the postmortem brain of a 65-year-old woman. The brain was then cut into ultrathin slices. The scientists stained the sections and then imaged them one by one on a flatbed scanner. Alan Evans and his coworkers at the Montreal Neurological Institute organized the 7,404 resulting images into a data set about a terabyte in size. Slicing had bent, ripped, and torn the tissue, so Evans had to correct these defects in the images. He also aligned each one to its original position in the brain. The result is mesmerizing: a brain model that you can swim through, zooming in or out to see the arrangement of cells and tissues.

At the start of the 20th century, a German neuroanatomist named Korbinian Brodmann parceled the human cortex into nearly 50 different areas by looking at the structure and organization of sections of brain under a microscope. “That has been pretty much the reference framework that we’ve used for 100 years,” Evans says. Now he and his coworkers are redoing ­Brodmann’s work as they map the borders between brain regions. The result may show something more like 100 to 200 distinct areas, providing scientists with a far more accurate road map for studying the brain’s different functions.

“We would like to have in the future a reference brain that shows true cellular resolution,” says Amunts—about one or two micrometers, as opposed to 20. That’s a daunting goal, for several reasons. One is computational: Evans says such a map of the brain might contain several petabytes of data, which computers today can’t easily navigate in real time, though he’s optimistic that they will be able to in the future. Another problem is physical: a brain can be sliced only so thin.

Advances could come from new techniques that allow scientists to see the arrangement of cells and nerve fibers inside intact brain tissue at very high resolution. Amunts is developing one such technique, which uses polarized light to reconstruct three-­dimensional structures of nerve fibers in brain tissue. And a technique called Clarity, developed in the lab of Karl Deisseroth, a neuroscientist and bioengineer at Stanford University, allows scientists to directly see the structures of neurons and circuitry in an intact brain. The brain, like any other tissue, is usually opaque because the fats in its cells block light. Clarity melts the lipids away, replacing them with a gel-like substance that leaves other structures intact and visible. Though Clarity can be used on a whole mouse brain, the human brain is too big to be studied fully intact with the existing version of the technology. But Deisseroth says the technique can already be used on blocks of human brain tissue thousands of times larger than a thin brain section, making 3-D reconstruction easier and less error prone. And Evans says that while Clarity and polarized-light imaging currently give fantastic resolution to pieces of brain, “in the future we hope that this can be expanded to include a whole human brain.”

—Courtney Humphries

La velocidad de rendimiento cognitivo entra en declive a partir de los 24 años

 

 

El cerebro al desnudo

A los 24 años no solo dejamos de ser adolescentes, sino que según un nuevo estudio de la Universidad Simon Fraser (Canadá), una persona alcanza su punto máximo en términos de desarrollo motor y cognitivo a esta edad. A partir de aquí, comienza a experimentar un declive.

El estudio, publicado en la revista Plos One, trataba de averiguar en qué momento de la vida comenzamos a sufrir una bajada en todo lo relacionado con nuestras habilidades motoras y su relación con el rendimiento cognitivo. Para ello, los investigadores analizaron los registros de rendimiento online de 3.305 jugadores de Starcraft 2 (Blizzard) con edades comprendidas entre los 16 y los 44 años de edad.

Los registros de rendimiento de los jugadores online constituyen una base de datos muy valiosa, ya que representan miles de horas representativas de las estrategias cognitivas en tiempo real. Así, los investigadores pudieron analizar profundamente de qué forma respondieron los jugadores a sus oponentes y qué tiempo emplearon para reaccionar.

El examen del volumen total de datos arrojó que “después de los 24 años, los jugadores muestran una desaceleración en sus reacciones; esta disminución del rendimiento cognitivo estaba presente incluso en los jugadores con más habilidad”, afirma Joe Thompson, autor principal del estudio.

De cualquier forma, los resultados también sugieren que aunque nos volvamos más lentos de respuesta con la edad, la experiencia adquirida con los años nos ayuda a desenvolvernos con más eficiencia y por tanto compensar esta pérdida de velocidad provocada por la edad.

 

Genetic Maps of the Brain Lead to Surprises

 

By Ed Lein and Mike Hawrylycz

The first detailed map of what our genes are doing inside our brains show how very different we are from mice and challenge a long-held theory of how our gray matter works

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As you read these words, your eyes scan the page, picking up patterns to which your mind assigns meaning. Meanwhile your heart contracts and relaxes, your diaphragm rises and drops to control your breathing, your back muscles tense to maintain your posture, and a thousand other basic tasks of conscious and subconscious life proceed, all under the coordinated control of roughly 86 billion neurons and an equal number of supporting cells inside your skull. To neuroscientists like us, even the simple act of reading a magazine is a wondrous feat—as well as an example of perhaps the hardest problem in science today: in truth, we cannot yet fully explain how the human brain thinks and why the brain of a monkey cannot reason as we do.

Neuroscientists have intensely studied the human brain for more than a century, yet we sometimes still feel like explorers who have landed on the shores of a newly discovered continent. The first to arrive plotted the overall boundaries and contours. In the early 1900s German scientist Korbinian Brodmann sliced up human brains and placed them under his microscope to examine the cerebral cortex—the exterior layers of gray matter that handle most perception, thought and memory. He parceled this cortex into several dozen regions based on the topology of the organ and how the cells in each area appear when labeled with various stains.