An On-Off Switch for Anxiety

Light control: Scientists use fiber optics to control genetically engineered neurons in the brains of animals (as shown here).    Credit: Deisseroth lab

 

 

Researchers discover a brain circuit that can instantly dampen—or exacerbate—anxiety in mice.

 

 

MIT Technology Review, March 24, 2011, by Emily Singer  —  With the flick of a precisely placed light switch, mice can be induced to cower in a corner in fear or bravely explore their environment. The study highlights the power of optogenetics technology—which allows neuroscientists to control genetically engineered neurons with light—to explore the functions of complex neural wiring and to control behavior.

 

In the study, Karl Deisseroth and collaborators at Stanford University identified a specific circuit in the amygdala, a part of the brain that is central to fear, aggression, and other basic emotions, that appears to regulate anxiety in rodents. They hope the findings, published today in the journal Nature, will shed light on the biological basis for human anxiety disorders and point toward new targets for treatment.

 

“We want to conceptualize psychiatric disease as real physical entities with physical substrates,” says Deisseroth. “Just like people who have asthma have reactive airways, people with anxiety disorders may have an underactive projection in the amygdala.”

 

The researchers engineered mice to express light-sensitive proteins in specific cells in the amygdala that send out neural wires, known as axons, to different substructures. Using a specially designed fiber-optic cable implanted in the animal’s brain, researchers found that aiming the light to activate one specific circuit had an immediate and potent effect on the animal’s behavior.

 

“I’ve never seen anything like it,” says Kay Tye, a postdoctoral researcher in Deisseroth’s lab and lead author on the study. Mice are naturally fearful of exploring open areas, she explains. Under normal circumstances, the animal “will poke its nose out and then scurry into a corner,” says Tye. “But when you turn on the light, the animal begins exploring the platform with no visible signs of anxiety. Then you turn the light off, and it scurries back in to the corner.”

 

The researchers could induce the opposite effect using a light-sensitive protein that silences the cells instead of activating them.

 

Shining light on the bodies of the cells, which in turn activates axons in multiple circuits, had no effect on the animals’ behavior, highlighting how important it is to be able to target individual circuits in the brain.

 

 

Video

New research bring scientists one step closer to isolating the mechanisms by which the brain compensates for disruptions and reroutes neural functioning — which could ultimately lead to treatments for cognitive impairments in humans caused by disease and aging. (Credit: iStockphoto/Vasiliy Yakobchuk)

 

 

 

University of Michigan Health System, March22, 2011  —  When Geoffrey Murphy, Ph.D., talks about plastic structures, he’s not talking about the same thing as Mr. McGuire in The Graduate. To Murphy, an associate professor of molecular and integrative physiology at the University of Michigan Medical School, plasticity refers to the brain’s ability to change as we learn.

Murphy’s lab, in collaboration with U-M’s Neurodevelopment and Regeneration Laboratory run by Jack Parent, M.D., recently showed how the plasticity of the brain allowed mice to restore critical functions related to learning and memory after the scientists suppressed the animals’ ability to make certain new brain cells.

The findings, published online this week in the Proceedings of the National Academy of Sciences, bring scientists one step closer to isolating the mechanisms by which the brain compensates for disruptions and reroutes neural functioning — which could ultimately lead to treatments for cognitive impairments in humans caused by disease and aging.

“It’s amazing how the brain is capable of reorganizing itself in this manner,” says Murphy, co-senior author of the study and researcher at U-M’s Molecular and Behavioral Neuroscience Institute. “Right now, we’re still figuring out exactly how the brain accomplishes all this at the molecular level, but it’s sort of comforting to know that our brains are keeping track of all of this for us.”

In previous research, the scientists had found that restricting cell division in the hippocampuses of mice using radiation or genetic manipulation resulted in reduced functioning in a cellular mechanism important to memory formation known as long-term potentiation.

But in this study, the researchers demonstrated that the disruption is only temporary and within six weeks, the mouse brains were able to compensate for the disruption and restore plasticity, says Parent, the study’s other senior author, a researcher with the VA Ann Arbor Healthcare System and associate professor of neurology at the U-M Medical School.

After halting the ongoing growth of key brain cells in adult mice, the researchers found the brain circuitry compensated for the disruption by enabling existing neurons to be more active. The existing neurons also had longer life spans than when new cells were continuously being made.

“The results suggest that the birth of brain cells in the adult, which was experimentally disrupted, must be really important — important enough for the whole system to reorganize in response to its loss,” Parent says.

Additional Authors: Benjamin H. Singer, Ph.D., Amy E. Gamelli, Ph.D., Cynthia L. Fuller, Ph.D., Stephanie J. Temme, all of U-M

The research was supported by grants from the National Institutes of Health, National Institute on Aging, National Institute of Neurological Disorders and Stroke. Temme is a National Science Foundation Graduate Research Fellow and was also supported by a U-M Rackham Merit Fellowship.

Journal Reference:

1.                         B. H. Singer, A. E. Gamelli, C. L. Fuller, S. J. Temme, J. M. Parent, G. G. Murphy. Compensatory network changes in the dentate gyrus restore long-term potentiation following ablation of neurogenesis in young-adult mice. Proceedings of the National Academy of Sciences, 2011; DOI: 10.1073/pnas.1015425108

 

Wearable PET: A rat’s head fits in the circular opening of this device, which is surrounded by miniaturized detectors and electronics. Credit: Brookhaven National Laboratory

 

 

Device maps the chemistry of the whole brain in moving animals.

 

 

MIT Technology Review, March 24, 2011, by Katherine Bourzac  —  A tiny wearable scanner has been used to track chemical activity in the brains of unrestrained animals for the first time. By revealing neurological circuitry as the subjects perform normal tasks, researchers say, the technology could greatly broaden the understanding of learning, addiction, depression, and other conditions.

The device was designed to be used with rats—the main animal model used by behavioral neuroscientists. But the researchers who developed the device, at Brookhaven National Laboratory, say it would be straightforward to engineer a similar device for people.

Positron emission tomography, or PET, is already broadly used in neuroscience research and in clinical treatment. It allows researchers to track the location of radioactively labeled neurotransmitters (the chemicals that carry signals between neurons) or drugs within the brain. Images of the way neurotransmitters and drugs move through the brain can reveal the processes that underpin normal behavior such as learning as well as pathologies including addiction. PET has been used to map drug-binding sites in the brains of addicts and healthy people, and to study how those sites change over time and with therapy.

A conventional PET scanner is so large that these studies have to be performed with the subject lying inside a large tube. Large photomultiplier tubes amplify signals from gamma rays emitted by labeled chemicals in the brain. The signals then pass through a desk-sized rack of electronics that process them and map them to a particular region of the brain. To get good readings during animal studies, the subjects are typically anaesthetized or restrained. What’s being measured is not normal waking behavior.

“We have very limited data about what brains do in the real world,” says Paul Glimcher, professor of neuroscience, economics, and psychology at New York University. Glimcher was not involved with the work.

The new portable scanner is designed to provide the same information about brain chemistry while an animal behaves naturally. It is small and lightweight enough that a rat can carry it around on its head. “[The rat] can move freely, interact with other animals, and at the same time we can make a 3-D map of, for example, dopamine receptors throughout the brain,” says David Schlyer, a senior scientist at Brookhaven who led the work.

Schlyer’s group worked for years to engineer a miniature PET scanner that could be worn by a moving subject. The device consists of a metal ring hanging from a support structure that helps support its weight and allows the rat to move around. The rat’s head goes inside the ring, which contains both detectors and electronics.

The key to miniaturizing the device, Schlyer says, was integrating all the electronics for each detector in the ring on a single, specialized chip. An avalanche photodiode also replaces the large photomultiplier tubes of conventional PET, amplifying the signals emitted by the labeled chemicals in the brain. “The rats take about an hour to acclimate, then begin behaving normally,” says Schlyer. The Brookhaven device is described this week in the journal Nature Methods.

The Brookhaven group used the scanner to map the dopamine receptors throughout the entire brains of of moving rats for the first time. Other groups, including Glimcher’s, have previously used invasive probes to study dopamine levels in cubic-millimeter-sized portions of the brain in unrestrained animals, but have not been able to look at the entire brain.

Glimcher describes one of several experiments that could be done with the portable device. Researchers know that addicts who have successfully completed rehab are at great risk of relapse if they visit the places they associate with the drug, probably because their brain has been chemically rewired to respond to these associations. Glimcher imagines studies in rats that map brain chemistry when the animals are allowed to decide whether or not to take a drug, and when they wander into a location they have learned to associate with the drug.

“We don’t really understand that well how circuits in [different parts of the brain] interact in addiction,” says Glimcher. “To even get to a place where I can give you a clinical hypothesis, we have got to get more basic information. This is the breakthrough that could make that possible.”

PET is not as broadly used in studies involving people as other neuroimaging methods because of the small but significant exposure to radiation that’s necessary. Still, the Brookhaven researchers say it would be possible to make a wearable PET scanner that fits inside something resembling a football helmet. Joseph Huston, chair of the Center for Behavioral Neurosciences at the University of Düsseldorf, says the Brookhaven group has done “an incredible service” to the neuroscience community in developing the device. “The rat is the most important model for the brain—everything basic [we know] about learning, feeding, fear, sex, is based on work in the rat.”

Schlyer says his group has talked with a few companies about licensing a commercial version of the device. But for now, they are mainly planning further behavioral studies in their lab. Mapping dopamine in waking animals could provide insights into a wide range of normal and pathological conditions such as the movement problems associated with Parkinson’s disease. But dopamine is just one of the many brain chemicals the group can map. Schlyer says they will also study the sexual behavior of rats.

The group is also working on another instrument that combines PET with magnetic resonance imaging to provide richer information about tissue structure and function. They will start a clinical trial of this device in breast cancer patients next month.

In the field of radiation oncology, the CyberKnife® Robotic Radiosurgery System is universally recognized as the premier radiosurgery system capable of delivering high doses of radiation with sub-millimeter accuracy anywhere in the body. As validated and proven in numerous peer-reviewed publications, the precision and accuracy of the system combines with continual image guidance and robotic mobility to deliver treatments characterized by high conformality and steep dose gradients.

The newest addition to the CyberKnife product line, the CyberKnife VSI™ System, continues Accuray’s tradition of innovation. Building on a foundation of accuracy and precision in radiosurgery, the CyberKnife VSI System extends these benefits to fractionated high precision radiation therapy with Robotic IMRT™ that can be delivered anywhere in the body.

All treatment options, from robotic radiosurgery to conventionally fractionated Robotic IMRT, are delivered using a seamless, fully-integrated and intuitive workflow. The clinical accuracy, routine non-coplanar delivery, robotic mobility and the best-in-class target tracking are leveraged when delivering any fractionation scheme. Extremely complex planning objectives do not have to be compromised in order to achieve scheduling objectives – the most demanding treatments can be delivered in a time slot that maximizes patient comfort as well as department throughput. The combination of rapid treatment times, support for treatment regimens that span the full spectrum of fractionation and the highest quality treatments ultimately attract a new patient population to the clinic.

The CyberKnife VSI System expands the capabilities of the CyberKnife System in the treatment of cancer. With nearly five hundred peer-reviewed publications and a rapidly increasing number of treated patients, the growing community of CyberKnife users is discovering more applications that can be helped by the technological edge and flexibility the CyberKnife System provides.

 

The main features of the CyberKnife system, shown on a Fanuc robot

 

The CyberKnife is a frameless robotic radiosurgery system invented by John R. Adler, a Stanford University Professor of Neurosurgery and Radiation Oncology, and Peter and Russell Schonberg of Schonberg Research Corporation. The two main elements of the CyberKnife are (1) the radiation produced from a small linear particle accelerator and (2) a robotic arm which allows the energy to be directed at any part of the body from any direction.

The CyberKnife system is a method of delivering radiotherapy, with the intention of targeting treatment more accurately than standard radiotherapy. It is not widely available, although the number of centres offering the treatment around the world has grown in recent years to over 150, particularly centered in North America, East Asia and Europe – the first UK CyberKnife was opened at The Harley Street Clinic in February 2009.

The CyberKnife system is sold by the company Accuray, located in Sunnyvale, California. The CyberKnife system is used for treating benign tumors, malignant tumors and other medical conditions.

 

Main features

Several generations of the CyberKnife system have been developed since its initial inception in 1990. There are two essential features of the CyberKnife system that set it apart from other stereotactic therapy methods.

Robotic mounting

The first is that the radiation source is mounted on a general purpose industrial robot. The original CyberKnife used a Japanese Fanuc robot, however the more modern systems use a German KUKA KR 240. Mounted on the Robot is a compact X-band linac that produces 6MV X-ray radiation. The linac is capable of delivering approximately 600 cGy of radiation each minute – a new 800 cGy / minute model was announced at ASTRO 2007. The radiation is collimated using fixed tungsten collimators (also referred to as “cones”) which produce circular radiation fields. At present the radiation field sizes are: 5, 7.5, 10, 12.5, 15, 20, 25, 30, 35, 40, 50 and 60 mm. ASTRO 2007 also saw the launch of the IRIS variable-aperture collimator which uses two offset banks of six prismatic tungsten segments to form a blurred regular dodecagon field of variable size which eliminates the need for changing the fixed collimators. Mounting the radiation source on the robot allows near-complete freedom to position the source within a space about the patient. The robotic mounting allows very fast repositioning of the source, which enables the system to deliver radiation from many different directions without the need to move both the patient and source as required by current gantry configurations.

Image guidance

The image guidance system is the other essential item in the CyberKnife system. X-ray imaging cameras are located on supports around the patient allowing instantaneous X-ray images to be obtained.

6D skull

The original (and still utilized) method is called 6D or skull based tracking. The X-ray camera images are compared to a library of computer generated images of the patient anatomy. Digitally Reconstructed Radiographs (or DRR’s) and a computer algorithm determines what motion corrections have to be given to the robot because of patient movement. This imaging system allows the CyberKnife to deliver radiation with an accuracy of 0.5mm without using mechanical clamps attached to the patient’s skull. The use of the image guided technique is referred to as frameless stereotactic radiosurgery. This method is referred to as 6D because corrections are made for the 3 translational motions (X,Y and Z) and three rotational motions. It should be noted that it is necessary to use some anatomical or artificial feature to orient the robot to deliver X-ray radiation, since the tumor is never sufficiently well defined (if visible at all) on the X-ray camera images.

6D Skull tracking

Xsight

Additional image guidance methods are available for spinal tumors and for tumors located in the lung. For a tumor located in the spine, a variant of the image guidance called Xsight-Spine is used. The major difference here is that instead of taking images of the skull, images of the spinal processes are used. Whereas the skull is effectively rigid and non-deforming, the spinal vertebrae can move relative to each other, this means that image warping algorithms must be used to correct for the distortion of the X-ray camera images.

A recent enhancement to Xsight is Xsight-Lung which allows tracking of some lung tumors without the need to implant fiduciary markers.

Fiducial

For soft tissue tumors, a method known as fiducial tracking can be utilized. Small metal markers (fiducials) made out of gold for bio-compatibility and high density to give good contrast on X-ray images are surgically implanted in the patient. This is carried out by an interventional radiologist, or neurosurgeon. The placement of the fiducials is a critical step if the fiducial tracking is to be used. If the fiducials are too far from the location of the tumor, or are not sufficiently spread out from each other it will not be possible to accurately deliver the radiation. Once these markers have been placed, they are located on a CT scan and the image guidance system is programmed with their position. When X-ray camera images are taken, the location of the tumor relative to the fiducials is determined, and the radiation can be delivered to any part of the body. Thus the fiducial tracking does not require any bony anatomy to position the radiation. Fiducials are known however to migrate and this can limit the accuracy of the treatment if sufficient time is not allowed between implantation and treatment for the fiducials to stabilize.

Synchrony

The final technology of image guidance that the CyberKnife system can use is called the Synchrony system. The Synchrony system is utilized primarily for tumors that are in motion while being treated, such as lung tumors and pancreatic tumors.

The synchrony system uses a combination of surgically placed internal fiducials, and light emitting optical fibers (markers) mounted on the patient skin. Since the tumor is moving continuously, to continuously image its location using X-ray cameras would require prohibitive amounts of radiation to be delivered to the patients skin. The Synchrony system overcomes this by periodically taking images of the internal fiducials, and predicting their location at a future time using the motion of the markers that are located on the patient’s skin. The light from the markers can be tracked continuously using a CCD camera, and are placed so that their motion is correlated with the motion of the tumor.

A computer algorithm creates a correlation model that represents how the internal fiducial markers are moving compared to the external markers. The Synchrony system is therefore continuously predicting the motion of the internal fiducials, and therefore the tumor, based on the motion of the markers. The correlation model can be updated at any time if the patient breathing becomes in any way irregular. The advantage of the Synchrony system is that no assumptions about the regularity or reproducibility of the patient breathing have to be made.

To function properly, the Synchrony system requires that for any given correlation model there is a functional relationship between the markers and the internal fiducials. The external marker placement is also important, and the markers are usually placed on the patient abdomen so that their motion will reflect the internal motion of the diaphragm and the lungs.

RoboCouch

A new robotic six degree of freedom patient treatment couch called RoboCouch has been added to the CyberKnife which provides the capability for significantly improving patient positioning options for treatment.

SmartPlanet.com, March 24, 2011, by Melissa Mahony  —  I rode my bike to Brooklyn Bridge Park’s newest bit of greenery last night. It wasn’t the onset of spring, but an electric vehicle charging station that runs on solar power.

I’ve actually passed by it a few times without realizing what it was. Comprised of two re-purposed shipping containers stacked together, the structure holds an array of 24 photovoltaic panels angled up from one end for southern exposure. The 5.6-kilowatt solar station powers the park’s fleet of 5 electric service vehicles and their electric Mini Cooper, the MINI E.

One concern regarding a possible EV revolution is where the electricity will originate. While many grids across the country offer at least some mix of power from renewable and traditional sources, filling an EV with electricity from coal-fire plants isn’t exactly Earth-friendly.

The charges from this station in Brooklyn come only from the sun.

Beautiful Earth Group (BE) recently donated the station to the park, bringing the portable building (it’s collapsible!) from nearby Red Hook to its new home. This 85-acre swath of land in the shadow of the Brooklyn Bridge has changed much in recent years, transforming from an industrial eyesore on the East River to well, one of my favorite places.

 

I spoke with David Gibbs, an engineer for BE. Gibbs said the off-grid station’s capacity couldn’t go as far as lighting the greenspace’s many lampposts, but it could take on more EVs and fill some power needs for park maintenance. For the park’s dark nights and cloudy days, a battery bank (at right) from the Trojan Battery Company will store the solar power.

According to the Brooklyn-based company, the station could save Brooklyn Bridge Park $200,000 in gas money over the project’s 25 years. They say it will also cut electricity costs by tens of thousands of dollars. In another measurement of value, it will offset an estimated 530 tons of carbon dioxide emissions. The project supports the PlaNYC initiative, which aims to cut the city’s carbon emissions 30 percent by 2030.

The move to combine the solar power and electric vehicle industries, however, doesn’t end under the bridge. I wrote last summer of a similar effort to shade parking lots with “solar trees.” The California start-up Envision Solar has since been integrating EV charging within solar parking spaces that it has provided for a handful of companies around the country.

In his NY Times blog, Jim Motavalli reports the concept for solar EV chargers is also sprawling out to the suburbs. A Metro-North train station in Westport, Connecticut has begun planning for a 30-kilowatt solar set-up. The idea is to charge EVs while their drivers continue with their commute on the train. Different from the Brooklyn Bridge Park facility, this one would be able to sell electricity back to the grid when not needed.

http://www.smartplanet.com/business/blog/intelligent-energy/a-solar-ev-station-grows-in-brooklyn/5323/