21 Nov 2012

Brain waves used to create music

Science and art often go hand in hand. M.C. Escher played with geometry in his famous prints of impossible realities, and anatomist Gunther von Hagenst captivated millions of people with a display of preserved human corpses and body parts. More recently, a popular installation at the London Barbican Gallery offers art lovers the unique experience of walking in the rain without getting wet. 

Science lets art push boundaries, and so is increasingly used by modern artists to shock and awe. But this is a two way street.

Researchers from the University of Electronic Science and Technology in China have now used recordings from brain scans to create music, and they hope that listening to the brain will give new insights into how it works.

EEG-fMRI music from two subjects (Credit: Lu et al 2012 PLoS ONE)

This unusual way of blending science and art was first introduced in 1965 by the American composer Alvin Lucier in the piece Music for Solo Performer, but it was not until the 1990s that 'brainwave music' boomed with the development of powerful computers. Scientists and musicians now use computational models to convert data from brain scan technology into music played by electronic synthesizers.

In the new study published in PLoS ONE, Jing Lu and colleagues developed a new method to combine readings from electroencephalograms (EEGs) and functional MRI (fMRI) brain scans to produce music that better mimics contemporary classical music. The amplitude and the frequency of the EEG signal were used to create the pitch and the duration of each musical note. This was then remixed with an fMRI signal, which set the intensity of the notes played. 

Functional MRI imaging (Credit: Wikipedia)

The authors acknowledge that the sources of the two signals are however unrelated. "There is something a little arbitrary about putting EEG and fMRI together in this way" says philosopher Dan Lloyd from Trinity College, Connecticut, who was the first person to create music from fMRI scans. "But you have to start somewhere, learning scales before you play a sonata, and this is a good start" he adds.

EEGs measure the electrical activity of the brain. Brain cells, or neurons, communicate with one another through electrical signals. During an EEG, electrodes are attached to the scalp and plugged into a computer that converts the electrical signals to waves. EEGs are currently used to diagnose epilepsy and sleep disorders for instance.

fMRI, or functional magnetic resonance imaging, on the other hand measures brain activity by detecting changes in blood flow, and is mostly used in research. Neurons need oxygen to make energy, so when a brain area is more active, oxygen-rich blood surges. The pattern of brain activity across the brain is then represented in a color code.

The authors of the study plan to improve their EEG-fMRI method so it may be used for clinical diagnosis, for example, if the music could produce audible differences between healthy and sick brains. Lloyd says

"With the proper sonification [conversion to sound], something like a 'brain stethoscope' could be developed as a clinical tool for detecting clues to a variety of brain conditions". 

But there are skeptics. David Sulzer, a neurophysiologist at Columbia University and jazz musician, thinks that brainwave music can only detect very significant changes in brain activity, such as an epileptic seizure. He says "If you cannot diagnose an illness through a chart recorder readout, I do not understand how it can be done sonically". 

Sulzer believes music made from brain activity is an art and a science didactic tool. For instance, he uses The Brainwave Music Project to teach the public about brain function before his performances of brainwave music.

Whether brainwave music will be useful for science or medicine remains an open question, but it can surely be said that it has become an art form of its own. It might not be for everyone's taste but brainwave music certainly causes an impression, which is the very definition of modern art.

Lu J, Wu D, Yang H, Luo C, Li C, et al. (2012) Scale-Free Brain-Wave Music from Simultaneously EEG and fMRI Recordings. PLoS ONE doi:10.1371/journal.pone.0049773

Listen to the authors' EEG-fMRI brainwave music here and here.

This article was published in The Munich Eye on 22-11-2012. You can read it here.

20 Nov 2012

Bacteria make living electric cables

At the bottom of the ocean, there is a strange world of microbes thriving in mud sediments. They all strive toward the same vital goal of using oxygen and available nutrients to produce energy for growth, so competition is fierce.
The bacteria on the seabed surface are the lucky ones, as they can readily take up oxygen from sea water. But a couple of centimeters below oxygen is scarce, and bacteria buried deep into the mud need to come up with more ingenious ways to gain energy.
Bacteria cables in the sea bed mud
(Credit: Mingdong Dong, Jie Song and Nils Risgaard-Petersen) 

In a new study published in Nature, a research team led by Nils Risgaard-Petersen and Lars Nielsen at Aarhus University in Denmark, shows how some bizarre bacteria employ a cunning trick to both feed from nutrients in deep marine sediment and consume oxygen at the surface: they function as living electric cables.

A couple of years ago, the team made the astonishing discovery that electric currents linked oxygen consumption at the top sediment layers with hydrogen sulfide at the bottom, more than a centimeter away. "The identity of the electron conductor has however been an enigma" Risgaard-Petersen says.
The scientists postulated that bacteria could work together to conduct these electric currents through a network of tiny hair-like appendages called nanowires. However, evidence so far shows that bacterial nanowires can only transfer electrons over shorter distances, so this alone could not explain the intriguing results.
To solve this riddle, Risgaard-Petersen and colleagues collected samples of marine sediment from Aarhus bay and carefully scrutinized the top sediment layers. In a true eureka moment, they found tufts of entangled centimeter-long filamentous bacteria. "Before us nobody had hypothesized about its existence, so nobody had looked for it" says Risgaard-Petersen.
The filaments of bacteria stretch between the top and bottom sediment layers
(Credit: Nils Risgaard-Petersen)

The filamentous microbes turned out to be new members of the Desulfobulbaceae family, which includes bacteria capable of consuming hydrogen sulfide in deep sediment zones. This seemed like a good indication that these long bacteria filaments could be mediating the flow of electrons across distant sediment layers. Indeed, when the scientists cut the filaments, the electric currents stopped and the consumption of oxygen and hydrogen sulfide plunged.
"Risgaard-Petersen and collaborators linked the presence of bacterial filaments to the electrical coupling of the oxygen and sulfide layers in marine sediments, which are typically separated by millimeter to centimeter distances" says Gemma Reguera, a microbiologist from Michigan State University specialized in the study of sediment bacteria "These [distance] scales truly defy our current knowledge of biological electron transfer".
Each filament consists of many bacterial cells lined up in a long chain and surrounded by a shared outer membrane. Interestingly, this outer membrane has uniform ridges filled up with charged material running along the entire length of the filament. The authors of the study believe these ridges could be 'internal insulated wires' for driving the electron flow across sediment layers. However, these molecular details remain unclear.
A cross-section of four cable bacteria viewed with an transmission electron microscope
(Credit: Karen Thomsen)

Derek Lovley, an expert on electromicrobiology at the University of Massachusetts thinks that discovering the source of this 'potentially conductive material' is crucial. "As with the initial studies with [bacterial nanowires] there will be skeptics because they have not been able to measure long-range electron transport directly" and adds "It will be interesting to watch this story unfold."
More than tens of thousand kilometers of filamentous bacteria live in a single square meter of mud from the undisturbed seabed, so it is possible that this type of long-distance electron transport could be widespread in nature. The long filaments are however very fragile, and small disturbances such as sea waves could lead to 'fatal cable breakage'. Eric Roden, an expert on biogeochemistry at the University of Wisconsin notes "Whether or not such filamentous networks are actually present and active in natural sediments, where all sorts of mixing processes and other disturbances are common, remains to be determined".

Since the discovery of bacterial nanowires, several research teams have explored their potential biotechnological applications, for example, in bioelectronic devices or for electricity generation from renewable sources, such as waste. Could the filamentous bacteria potentially be used for technology development?

"We need to know more about how current is transported inside these organisms" explains Risgaard-Petersen "but perhaps there is a possibility to grow electric conductive structures for use in electrical devices".

This article was published in The Munich Eye on 26-10-2012. You can read it here.

Pfeffer, C. et al. Nature (2012) http://dx.doi.org/10.1038/nature11586

13 Nov 2012

Music lessons in childhood benefit adult brain

Parents may have found a new reason to encourage their children to play a musical instrument. A new study led by scientists at Northwestern University reports that musical training during childhood can have positive effects on the adult brain, even if the training only lasts a few years.                        

Credit: everystockphoto

As children return to school, many parents face the question of whether to enroll their child in music lessons. They don't want to overload their child with extracurricular activities, but they are also afraid of missing the age window when musical talent can be discovered and nurtured. Besides, an investment in music lessons might be fruitless if the child stops playing the musical instrument at a later age. Yet scientists now argue this is not the case.

Research on professional musicians shows that musical experience can not only rewire the auditory system, but also improve several of the brain's functions, such as motor control, memory and verbal ability. However, it had never been investigated whether these positive changes in the brain persist if the musical training stops before adulthood, which is indeed the case for most people who engage in music lessons at a young age.                        

In a new study published in August in the Journal of Neuroscience, scientists test healthy adults who started playing a musical instrument at around 9 years of age but stopped a few years later. They used a technique called Auditory Brainstem Response (ABR), which measures brain activity after auditory stimulation, a similar test to the one used to assess whether newborn babies can hear. The scientists then performed the same experiments on adults who have never played an instrument and compared the results. 

'We find that the adult brain profits from past experiences with music. This is the first study to focus on whether the effects of music are long-lasting and whether they persist after the child stops playing an instrument' explains Erika Skoe, leading author in the study.          

The authors of the study propose that these long-term positive changes in the brain could be a result of the active interaction with sound that occurs when playing a musical instrument. 'Playing a musical instrument is an incredibly active process that engages all of the senses, not just hearing. Active engagement with sound appears to be the critical ingredient for promoting long-lasting neural changes' says Skoe. This could explain why passive exposure to an enriched auditory environment alone only produces a temporary enhancement of brain activity, a phenomenon that has been observed in rat models. Referring to these experiments Skoe explains 'An enriched auditory environment was more or less "background music" in the animal's environment and not something that they could directly interact with.'

So when should children start learning music in order to benefit from these long-lasting neural changes?

'Our study suggests that long-lasting effects can be seen with just one year of music lessons during grade [primary] school. However, music is likely to be a positive force on the brain at any age. Because every child is different, we are cautious about interpreting our results too prescriptively' answers Skoe.

This and other studies raise the debate of whether or not music lessons should be compulsory in state schools. Nina Kraus, head of the Auditory Neuroscience Laboratory where the present study was conducted says 

'I think musical training can do tremendous good (beyond music) in developing a better learner. Musical training strengthens auditory-based communication and learning skills including hearing speech in noisy situations, reading, auditory working memory, and auditory attention.' 

From this elegant research we learn that playing a musical instrument during childhood has long-lasting positive effects on the brain. And the good news for parents is, that children will benefit from their music lessons throughout their adult life, even if they decide to swap the violin for a surfboard in their teens.

This article was published in The Munich Eye on 7-10-2012. You can read it here.

Skoe E. and Kraus N. Journal or Neuroscience (2012) DOI: 10.1523/JNEUROSCI.1949-12.2012

9 Nov 2012

Lung-on-a-chip: a human disease model that could revolutionize drug discovery

Scientists used a microchip that recreates a breathing lung to study pulmonary edema and test a new drug against this life-threatening disease, raising hopes that this organ-on-chip technology could speed up drug development and replace animal testing.

The lung-on-a-chip is the size of a memory stick and is made of a clear silicone rubber
 (credit: Harvard University Wyss Institute)

The lung-on-a-chip was first developed by Donald Ingber's team at the Harvard University Wyss Institute two years ago using technology from the computer microchip industry. The microdevice mimics the tiny air sacs in the lungs where gases are exchanged between the air we breathe and the blood.
About the size of a memory stick, the plastic microchip contains two chambers separated by a thin leaky membrane. This flexible membrane has living lung cells with air flowing through them stuck on one side, and blood vessel cells immersed in fluid on the other. Gases or fluids can be transferred across the membrane between lung and blood vessel tissues.
The membrane and attached cells are stretched and relaxed by a vacuum system in the same way as an air sac during breathing movements.

Now, in a study published this week in Science Translational Medicine, the Harvard scientists used these microchips to mimic pulmonary edema, showing for the first time that organs-on-chip can be used to model human disease. 

Pulmonary edema is the abnormal buildup of fluid in the lung air sacs, which leads to respiratory failure and if left untreated can be fatal. The most common cause of pulmonary edema is congenital heart failure, but it can also occur as a side effect of some drugs. 

In this study, the researchers used interleukin-2 (IL-2), a chemotherapy drug with severe side effects, to recapitulate pulmonary edema in the lung-on-a-chip. Injection of this drug into the microchip blood chamber triggered fluid leakage across the membrane into the air space, recreating what happens in the lungs of human patients treated with IL-2.

A chemotherapy drug recapitulates pulmonary edema in the microchip
 (credit: Harvard Institute Wyss Institute)
But there was a surprising result: the physical action of 'breathing' aggravated fluid leakage into the air chamber. IL-2 causes cell connections to break, which opens holes in the tissues. It turns out that the mechanical strain of the breathing motion dramatically increases the size of these holes. 'This truly changes the way we view this disease process, as well as how we might treat this type of condition' says Ingber.

This unexpected finding led the team to test an experimental drug developed by GlaxoSmithKline (GSK) which blocks a protein involved in controlling tissue mechanical tension. They found that the drug 'fully prevents the IL2-induced edema response'. In a collaborative study, a GSK research team led by Kevin Thorneloe showed that the drug curbed pulmonary edema symptoms caused by heart failure in animal models, confirming the lung-on-a-chip results.
Drug development is a long and costly process that currently relies on animal testing, and more often than not drugs that perform well in animal models then fail in the human clinical trial stages.
'Major pharmaceutical companies and government funding agencies are now beginning to recognize a crucial need for new technologies that can quickly and reliably predict drug safety and efficacy in humans in preclinical studies' says Ingber.

Human cells cultured in a three-dimensional matrix are widely used to test drug toxicity but they lack the complex properties that define organs, such as tissue-tissue interactions or mechanically active environments. Organs-on-chip could be the solution to this problem.
'Our finding that breathing motions are critical to mimic the IL-2 toxicity response is a clear example of how this could not be done with conventional culture models' says Ingber.

In the past years several groups have built organ-on-chips that mimic lung, kidney, heart and other organs, but this study is the first to model a human disease and to successfully test a drug in a microchip. Shuichi Takayama, an expert on biomedical engineering at the University of Michigan says
'This study demonstrates that this type of technology is promising for replacing animal models in some aspects of drug screening and testing.'

However, the organ-on-chip technology is in its early stages and Ingber believes 'animal models will be around for a long time'.

'The goal is to develop organ chip replacements for one particular animal model at a time, and hence, slowly shift the emphasis away from animal models. This would represent a major advance in the pharmaceutical field, and have great implications for testing of chemicals, toxins and cosmetics as well' he says.

This article was published in The Munich Eye on the 9-11-2012. You can read it here.

Huh et al Science Translational Medicine (2012) DOI: 10.1126/scitranslmed.3004249

3 Nov 2012

Promiscuous female guppies have the upper hand

New research shows that mating with multiple partners brings benefits for females. In a study published in September in the journal BMC Evolutionary Biology, scientists report that promiscuous female guppies are more fertile than singly mated females.

Female and male Trinidadian guppies
(credit: Biodiversity and Behavioural Group at University of St Andrews)

For evolutionary biologists, it is obvious why male promiscuity has selective advantages: mating with several females gives males more chances to fertilize eggs and produce viable descendants. However, female promiscuity, or polyandry (poly- many, andras- male), still stirs a debate in the scientific community, because it doesn't bring any apparent benefit for the females. On the contrary, multiple mating can come at a high cost. Besides consuming time and energy, multiple mating exposes females to predation, disease and physical harm from males. Female polyandry is nonetheless widespread in nature, and growing evidence shows that choosing to mate with several partners seems to be the rule, rather than the exception in a wide number of species, from invertebrates to birds, reptiles and even some mammals. 

So why do females prefer to mate with multiple males? Scientists believe that polyandry might have indirect genetic benefits for the females, ensuring the 'good genes' pass on to the next generation. For instance, in some species the offspring of promiscuous females is better adapted, and hence produces more grandchildren for the female, than ofspring from single mated females. However, in the study performed by Anne Magurran's team at the University of St Andrews in the UK, the researchers found that, unexpectedly, multiple mating brings direct benefits for females. 

The scientists performed controlled experiments in the laboratory with wild caught guppies from the Lower Tacarigua River in Trinidad. They placed about 80 females in individual tanks and then allowed them to mate either with a single male, or with multiple males. They carefully followed these guppies for two generations, keeping count of the number of children and grandchildren they produced. They found that promiscuous females had more offspring, but there was no difference in their size, growth rate or viability, when compared to offspring of single mated females. Miguel Barbosa who led the study says 'The surprise came when the results showed that the benefits of multiple mating were achieved through an increase in female fecundity rather than by increasing offspring viability/attractiveness, as expected.' 

Previous research showed a similar increase in fertility in promiscuous females of other species, but this is the first study where both direct and indirect benefits of multiple mating are investigated over two generations. But why is there an increase in fertility in multiply mated females? Barbosa explains 'The presence of sperm from multiple sources/fathers reduces the risk of genetic incompatibility, but also promotes sperm competition. Both can contribute to the increase in fecundity reported in our study.' 

Another surprising finding in this study was that promiscuous female guppies had more sons, and scientists believe this accounts for the larger number of grandchildren. 'There was 60% more sons produced by multiple mated females than produced by single mated ones' says Barbosa. This is the first evidence that female multiple mating influences the offspring sex-ratio in guppies, but the scientists, however, still don't understand what causes this overproduction of males. 

Tommaso Pizzari, an evolutionary biologist from the University of Oxford in the UK, says 'The present study offers experimental evidence suggesting that female promiscuity might be associated with some net fitness benefits to the female (...) These results contribute to shed light into a major evolutionary puzzle: namely, why do females mate with multiple males when often one insemination is sufficient for fertilization and mating is costly.'

This article was published in The Munich Eye on 02-10-2012. You can read it here.

Barbosa et al. BMC Evolutionary Biology (2012) DOI: 10.1186/1471-2148-12-185