Neuroscience

Researchers at the University of Southern California have devised a method for detecting certain neurological disorders through the study of eye movements.

In a study published today in the Journal of Neurology, researchers claim that because Attention Deficit Hyperactivity Disorder (ADHD), Fetal Alcohol Spectrum Disorder (FASD) and Parkinson’s Disease (PD) each involve ocular control and attention dysfunctions, they can be easily identified through an evaluation of how patients move their eyes while they watch television.

“Natural attention and eye movement behavior – like a drop of saliva – contains a biometric signature of an individual and her/his state of brain function or dysfunction,” the article states. “Such individual signatures, and especially potential biomarkers of particular neurological disorders which they may contain, however, have not yet been successfully decoded.”

Typical methods of detection—clinical evaluation, structured behavioral tasks and neuroimaging—are costly, labor-intensive and limited by a patient’s ability to understand and comply with instructions. To solve this problem, doctoral student Po-He Tseng and Professor Laurent Itti of the Department of Computer Science at the USC Viterbi School of Engineering, along with collaborators at Queen’s University in Canada, have devised a new screening method.

Participants in the study were simply instructed to “watch and enjoy” television clips for 20 minutes while their eye movements were recorded. Eye-tracking data was then combined with normative eye-tracking data and a computational model of visual attention to extract 224 quantitative features, allowing the team to use new machine learning techniques to identify critical features that differentiated patients from control subjects.

With eye movement data from 108 subjects, the team was able to identify older adults with Parkinson’s Disease with 89.6% accuracy, and children with either ADHD or FASD with 77.3% accuracy.

Providing new insights into which aspects of attention and gaze control are affected by specific disorders, the team’s method provides considerable promise as an easily-deployed, low-cost, high-throughput screening tool, especially for young children and elderly populations who may be less compliant to traditional tests.

“For the first time, we can actually decode a person’s neurological state from their everyday behavior, without having to subject them to difficult or time-consuming tests,” Itti said.

Source: University of Southern California

Nanoparticles often meet a sticky end in the brain. In theory, the tiny structures could deliver therapeutic drugs to a brain tumour, but navigating the narrow, syrupy spaces between brain cells is difficult. A spot of lubrication could help.

Nanoparticles (green) coated with poly(ethylene-glycol) (PEG) (Image: Elizabeth Nance, Graeme Woodworth, Kurt Sailor)

Justin Hanes at Johns Hopkins University in Baltimore, Maryland, was surprised to discover just how impermeable brain tissue is to nanoparticles. “It’s very sticky stuff,” he says, similar in adhesiveness to mucus, which protects parts of the body – such as the respiratory system – by trapping foreign particles.

It was thought that the adhesiveness of brain tissue limited the size of particles that can smoothly spread through the brain. Signalling molecules, nutrients and waste products below 64 nanometres in diameter can pass through the tissue with relative ease, but larger nanoparticles – suitable for delivering a payload of drugs to a specific location in the brain – quickly get stuck.

Now Hanes and his colleagues have doubled that size limit. They coated their nanoparticles with a densely-packed polymer shield, which lubricates their surface by preventing electrostatic and hydrophobic interactions with the surrounding tissue. “A nice hydrated shell around the particle prevents it from adhering to cells,” says Hanes.

Tracking the particles

Using this approach, they were able to observe the diffusion of nanoparticles 114 nanometres in diameter through live mouse brains and dissected human and rat brain tissue. Hanes believes the true upper size limit now lies somewhere between 114 nm and 200 nm. “Things were starting to slow down at 114,” he says.

But further research is needed before the team can progress to clinical trials in humans. “At this scale, it is very important to understand where our nanoparticles go once injected into the body,” says team member Elizabeth Nance, also of Johns Hopkins University. “We will need to show that, when combined with a therapeutic agent, these particles are getting to our site of interest, are having the intended effect and are not causing any side effects or toxicity to healthy normal tissue.”

"The effect of this work should be long-term," says Paul Wilson at the University of Warwick in Coventry, UK. The result represents significant progress in the battle to administer drugs within the brain, he says. "More effective and longer-lasting treatments against brain diseases, such as tumours and strokes, will no doubt soon follow."

Source: NewScientist

ScienceDaily (Aug. 28, 2012) — Deep-brain stimulation (DBS) may stop uncontrollable shaking in patients with Parkinson’s disease and essential tremor by imposing its own rhythm on the brain, according to two studies published recently by University of Alabama at Birmingham researchers in the journal Movement Disorders. An article addressing brain stimulation for essential tremor was published online August 28; a related article on Parkinson’s disease was released May 30.

DBS uses an electrode implanted beneath the skin to deliver electrical pulses into the brain more than 100 times per second. Although this technology was approved by the Food and Drug Administration more than 15 years ago, it remains unclear how it reduces tremor and other symptoms of movement disorders.

With the help of electroencephalography or EEG — electrodes placed on the scalp — study authors used new techniques to suppress the electrical signal associated with the DBS electrode. That enabled the first clear, non-invasive EEG measurements of the underlying brain response during clinically effective, high-frequency brain stimulation in humans.

The results show that nerves in the cerebral cortex, the outer layer of the brain, fire with rapid and precise timing in response to individual stimulus pulses. This suggests that DBS may synchronize the firing of nerve cells and break the abnormal rhythms associated with involuntary movements in Parkinson’s disease and essential tremor.

The newly identified rhythm was captured during effective DBS treatment, so it could represent a new physiological measure of the stimulation dose, say the authors. If validated, such a yardstick could help to guide the fine-tuning of DBS stimulator settings in patients for more lasting relief, fewer side effects and less-frequent battery-replacement surgeries.

"Though it’s clear that more work is needed to better understand these initial observations, we’re very excited by our findings because they may provide a biological marker for improvement in the symptoms of these patients," says Harrison Walker, M.D., assistant professor in the UAB Department of Neurology’s Division of Movement Disorders and lead author of the study.

In current clinical practice, stimulator settings are adjusted by trial and error, requiring careful observation of changes in symptoms over multiple clinic visits. But such immediate, visual feedback may not be available as DBS is applied to neurological or psychiatric conditions such as epilepsy, severe depression or obsessive compulsive disorder. In these diseases, an effective dose measurement could be especially useful in optimizing DBS therapy.

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Devices could reveal inner workings of neurons and how they communicate with each other.

Automated assistance may soon be available to neuroscientists tackling the brain’s complex circuitry, according to research presented last week at the Aspen Brain Forum in Colorado. Robots that can find and simultaneously record the activity of dozens of neurons in live animals could help researchers to reveal how connected cells interpret signals from one another and transmit information across brain areas — a task that would be impossible using single-neuron studies.

A robot that can access the internal workings of neurons could be scaled up to allow 100 cells to be studied at a time. MIT McGovern Institute/E. Boyden/Sputnik Animation

The robots are designed to perform whole-cell patch-clamping, a difficult but powerful method that allows neuroscientists to access neurons’ internal electrical workings, says Edward Boyden of the Massachusetts Institute of Technology in Cambridge, who is leading the work.

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ROBOTS developed in the safety of a laboratory can be too slow to react to the dangers of the real world. But software inspired by biology promises to give robots the equivalent of the mammalian amygdala, a part of the brain that responds quickly to threats.

(Image: SuperStock)

STARTLE, developed by Mike Hook and colleagues at Roke Manor Research of Romsey in Hampshire, UK, employs an artificial neural network to look out for abnormal or inconsistent data. Once it has been taught what is out of the ordinary, it can recognise dangers in the environment.

For instance, from data fed by a robotic vehicle’s on-board sensors, STARTLE could notice a pothole and pass a warning to the vehicle’s control system to focus more computing resources on that part of the road.

"If it sees something anomalous then investigative processing is cued; this allows us to use computationally expensive algorithms only when needed for assessing possible threats, rather than responding equally to everything," says Hook.

This design mimics the amygdala, which provides a rapid response to threats. The amygdala helps small animals to deal with complex, fast-changing surroundings, allowing them to ignore most sensory stimuli. “The key is that it’s for spotting anomalous conditions,” says Hook, “not routine ones.”

STARTLE has been tested in both vehicle navigation and robot health monitoring. In the latter, it can be trained to respond to danger signs, such as sudden changes in battery power or temperature. It has also been tested in computer networks, as a way to detect security threats, having been trained to identify the pattern of activity associated with an attack.

"A robot amygdala network could be useful," says neuroscientist Keith Kendrick of the University of Electronic Science and Technology of China in Chengdu. "Such a low-resolution analysis will sometimes make mistakes, and you will avoid something needlessly." But a slower, high-resolution analysis is also carried out, he says, which can override the mistakes.

Hooks says that STARTLE could be useful for any robots in complex environments. For example, a robot vehicle would be able to spot other drivers behaving erratically, a major challenge for conventional computing.

Source: NewScientist

Columbia neurophysiologist David Sulzer took his first piano lessons at the age of 11 and was playing his violin and guitar in bars by age 15. Later he gained a national following as a founder of the Soldier String Quartet and the Thai Elephant Orchestra—an actual orchestra of elephants in northern Thailand—and for playing with the likes of Bo Diddley, the Velvet Underground’s John Cale and the jazz great Tony Williams.

From left, Brad Garton and David Sulzer discuss turning brain waves into music on WHYY/PBS in Philadelphia.

It was only after arriving at Columbia, however, that the musician-turned-research-scientist embarked on perhaps his most exotic musical venture—using a computer to translate the spontaneous patterns of his brain waves into music.

With the help of Brad Garton, director of Columbia’s Computer Music Center, Sulzer has performed his avant-garde brain wave music in solo recitals and with musical ensembles.

Last spring, Sulzer presented a piece entitled Reading Stephen Colbert at a conference in New York City sponsored by Columbia and the Paris-based IRCAM (Institut de Recherche et Coordination Acoustique/Musique), a global center of musical research.

Sulzer, a professor in the departments of Psychiatry, Neurology and Pharmacology, wore electrodes attached to his scalp to measure voltage fluctuations in his brain as he sat in a chair reading a book by the comedian. Those fluctuations were fed into a computer program created by Garton, which transformed them into musical notes.

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Are you a morning lark or a night owl? Scientists use that simplified categorization to explain that different people have different internal body clocks, commonly called circadian clocks. Sleep-wake cycles, digestive activities, and many other physiological processes are controlled by these clocks. In recent years, researchers have found that internal body clocks can also affect how patients react to drugs. For example, timing a course of chemotherapy to the internal body time of cancer patients can improve treatment efficacy and reduce side effects.

Round the clock. Tracking the levels of 50 hormones and amino acids in blood samples (shown by ribbons) reveals a body’s internal time. Credit: PNAS

But physicians have not been able to exploit these findings because determining internal body time is, well, time consuming. It’s also cumbersome. The most established and reliable method requires taking blood samples from a patient hourly and tracking levels of the hormone melatonin, which previous research has tied closely to internal body time.

Now a Japanese group has come up with an alternative method of determining internal body time by constructing what it calls a molecular timetable based on levels in blood samples of more than 50 metabolites—hormones and amino acids—that result from biological activity. The researchers established a molecular timetable based on samples from three subjects and validated it using the conventional melatonin measurement. They then used that timetable to determine the internal body times of other subjects by checking the levels of the metabolites in just two blood samples from each subject per day.

Having such a timetable could allow doctors to synchronize drug delivery to internal body time, the team reports online today in the Proceedings of the National Academy of Sciences. “Usually personalized medicine is focusing on genetic differences, but there are also temporal differences [among patients]. That will be the next step in personalized medicine,” says systems biologist Hiroki Ueda of the RIKEN Center for Developmental Biology in Kobe, Japan, who heads the research group.

"In principle, the method holds great promise as a way of replacing the cumbersome melatonin assay," says Steven Brown, a molecular biologist at the University of Zurich in Switzerland. "The authors show in a small-scale, well-controlled experiment that they are able to predict internal body time within a precision frame of 3 hours," says Urs Albrecht of the University of Fribourg in Switzerland. Both researchers say further work will be necessary to make the technique more practical and more widely applicable, and Ueda agrees. The experimental subjects were all young men, and different molecular timetables are likely needed for women and for people of different ages. He would also like to improve the precision and make it reliable with just one blood sample per day.

Source: ScienceNOW

ScienceDaily (Aug. 27, 2012) — Muscular dystrophy is a complicated set of genetic diseases in which genetic mutations affect the various proteins that contribute to a complex that is required for a structural bridge between muscle cells and the extracellular matrix (ECM) that provides the physical and chemical environment required for their development and function.

The affects of these genetic mutations in patients vary widely, even when the same gene is affected. In order to develop treatments for this disease, it is important to have an animal model that accurately reflects the course of the disease in humans. In this issue of the Journal of Clinical Investigation, researchers at the University of Iowa report the development of a mouse model of Fukuyama’s muscular dystrophy that copies the pathology seen in the human form of the disease.

By removing the gene fukutin from mouse embryos at various points during development, researchers led by Kevin Campbell were able to determine that fukutin disrupts important modifications of dystrophin that prevent the muscle cells from attaching to the ECM. Disruption of the gene earlier in development led to a more severe form of the disease, suggesting that fukutin is important for muscle maturation. Disruptions in later stages of development caused a less severe form of the disease. In a companion piece, Elizabeth McNally of the University of Chicago discusses the implications of this disease model for the development of new therapies to treat muscular dystrophy.

Source: Science Daily