Posts tagged oscillations
Articles and news from the latest research reports.
Equations reveal the rebellious rhythms at the heart of nature
From the beating of our hearts to the proper functioning of our brains, many systems in nature depend on collections of ‘oscillators’; perfectly-coordinated, rhythmic systems working together in flux, like the cardiac muscle cells in the heart.
Unless they act together, not much happens. But when they do, powerful changes occur. Cooperation between neurons results in brain waves and cognition, synchronized contractions of cardiac cells cause the whole heart to contract and pump the blood around the body. Lasers would not function without all the atomic oscillators acting in unison. Soldiers even have to break step when they reach a bridge in case oscillations caused by their marching feet cause the bridge to collapse.
But sometimes those oscillations go wrong.
Writing in the journal Nature Communications, scientists at Lancaster University report the possibility of “glassy states” and a “super-relaxation” phenomenon, which might appear in the networks of tiny oscillators within the brain, heart and other oscillating entities.
To uncover these phenomena, they took a new approach to the solution of a set of equations proposed by the Japanese scientist Yoshiki Kuramoto in the 1970s. His theory showed it was possible in principle to predict the properties of a system as a whole from a knowledge of how oscillators interacted with each other on an individual basis.
Therefore, by looking at how the microscopic cardiac muscle cells interact we should be able to deduce whether the heart as a whole organ will contract properly and pump the blood round. Similarly, by looking at how the microscopic neurons in the brain interact, we might be able to understand the origins of whole-brain phenomena like thoughts, or dreams, or amnesia, or epileptic fits.
Physicists Dmytro Iatsenko, Professor Peter McClintock, and Professor Aneta Stefanovska have reported a far more general solution of the Kuramoto equations than anyone has achieved previously, with some quite unexpected results.
One surprise is that the oscillators can form “glassy” states, where they adjust the tempos of their rhythms but otherwise remain uncoordinated with each other, thus giving birth to some kind of “synchronous disorder” rather like the disordered molecular structure of window glass. Furthermore and even more astonishingly, under certain circumstances the oscillators can behave in a totally independent manner despite being tightly coupled together, the phenomenon the authors call “super-relaxation”.
These results raise intriguing questions. For example, what does it mean if the neurons of your brain get into a glassy state?
Dmytro Iatsenko, the PhD student who solved the equations, admitted the results posed more questions than they answered.
“It is not fully clear yet what it might mean if, for example, this happened in the human body, but if the neurons in the brain could get into a “glassy state” there might be some strong connection with states of the mind, or possibly with disease.”
Lead scientist Professor Aneta Stefanovska said: “With populations of oscillators, the exact moment when something happens is far more important than the strength of the individual event. This new work reveals exotic changes that can happen to large-scale oscillations as a result of alterations in the relationships between the microscopic oscillators. Because oscillations occur in myriads of systems in nature and engineering, these results have broad applicability.”
Professor Peter McClintock said: “The outcome of the work opens doors to many new investigations, and will bring enhanced understanding to several seemingly quite different areas of science.”
We’ve all heard about circadian rhythm, the roughly 24-hour oscillations of biological processes that occur in many living organisms. Yet for all its influence in many aspects of our lives — from sleep to immunity and, particularly, metabolism — relatively little is understood about the mammalian circadian rhythm and the interlocking processes that comprise this complex biological clock.
Through intensive analysis and computer modeling, researchers at UC Santa Barbara have gained insight into factors that affect these oscillations, with results that could lend themselves to circadian regulation and pharmacological control. Their work appears in the early edition of the Proceedings of the National Academy of Sciences.
“Our group has been fascinated with circadian rhythms for over 10 years now, as they represent a marvelous example of robust control at the molecular scale in nature,” said Frank Doyle, chair of UCSB’s Department of Chemical Engineering and the principal investigator for the UCSB team. “We are constantly amazed by the mechanisms that nature uses to control these clocks, and we seek to unravel their principles for engineering applications as well as shed light on the underlying cellular mechanisms for medical purposes.”
“Focus is often given to metabolism, cell division and other generic cell processes, but circadian oscillations are just as central to how life is organized,” said Peter St. John, a researcher in the Department of Chemical Engineering and lead author of the study.
Blood pressure, he noted, varies with time of day, as do visual acuity, smell and taste. Certain hormones are released at certain times to do their tasks. We get sleepy or become more alert at different hours. All these various highs and lows, rises and falls are the result of our circadian rhythm.
“There are genes and proteins that are expressed in a cell and their activity, or expression level, changes with time of day,” explained St. John. “These oscillations are caused by genetic circuits. So you’ll have a gene that’s produced, and when it’s in its finished form, it will turn itself off.” The proteins and genes get cleared away, after which production starts all over again, in a cycle that takes roughly 24 hours to complete.
While genetics plays a role in these rhythms — for instance if your parents were night owls, it’s likely you will be one too — environment, habits and lifestyles also affect the clock.
“It’s not just this free-running oscillator,” said St. John. “It gets these inputs from light. For instance if you get light early in the morning, it’ll speed up something so your phase is adjusted to the time of day.” Other influences include food (not so much what you eat but when), drugs, shift work and frequent travel across time zones.
The healthiest circadian rhythms are the ones that are considered to be “high-amplitude” — where different and complementary processes occur in the body during distinct and regular daytime and nighttime phases.
“We’re very different animals during the night and the day,” said St. John. “If you’re fasting at night and you’re asleep, the demands on your cells will be very different than if you’re awake and running around. There’s this temporal separation between the genes that you need during the day and those you need at night.”
Problems occur when the amplitude gets repressed, often because of modern-day schedules and lifestyles. Too much light at night, insufficient or irregular sleep hours, and eating or exercising too late in the evening are all habits that don’t allow for the necessary nighttime-phase cellular activity. This in turn can lead to disorders such as diabetes, heart disease and obesity. In very preliminary studies, Alzheimer’s disease and certain liver conditions are also associated with low-amplitude rhythms.
Establishing high-amplitude circadian rhythms could be as simple as modifying our schedules, but for some people — those with sleep disorders, for example, or those whose work requires long and irregular hours — it can be difficult, if not impossible.
By studying the regulation of the clock proteins called Period (PER) and Cryptochrome (CRY) — proteins that are thought to be involved with metabolism — St. John and Doyle were able to model the mechanisms of two small-molecule drugs — Longdaysin and KL0001 — that regulate the expression of the clock proteins. The insight they gained could lead to therapies that can help those with repressed circadian rhythms.
“Everybody thought that these were very similar proteins,” said St. John. “They bind to each other. They enter the nucleus together.” The assumption was that perturbations to those proteins would produce similar results. “But when we analyzed the data,” St. John continued, “it turned out that when you stabilize PER you get these higher-amplitude rhythms, but when you stabilize CRY you get these lower-amplitude rhythms.”
These results — obtained by studying cultured human cells that glow depending on their circadian phase, as well as through computer modeling — shed light on the mechanisms behind the metabolic aspect of circadian rhythms and pave the way for drug therapies that could decrease the risk of disease for those with disrupted rhythms. The UCSB researchers worked in collaboration with experimental scientists Tsuyoshi Hirota and Steve Kay from UC San Diego and USC, respectively.
“These collaborative partnerships with life scientists are crucial to the success of a project like this,” said Doyle, “and this kind of collaborative research team can implement the paradigm of systems biology with combined mathematical modeling and high-throughput experimental biology.”
Future modeling studies will try to determine if there is an optimal phase for taking one drug or the other to improve the amplitude of circadian rhythms. Experimental work will focus on improving specificity and bioavailability — the amount of drug that actually reaches the target tissues before being discharged by the body.
Crossing the channel: Surprising new findings in the neurology of sleep and vigilance
A recent neurological addressing one of the most fundamental issues in sleep rhythm generation study underscores an inconvenient truth—namely, that established scientific facts have and will continue to change. Researchers at Institute for Basic Science (Daejeon), Korea Institute of Science and Technology (Seoul) and Yonsei University (Seoul) have demonstrated significant exceptions to the theory, long accepted as dogma, that low-threshold burst firing mediated by T-type Ca2+channels in thalamocortical neurons is the key component for sleep spindles. (A T-type Ca2+channel is a type of voltage-gated ion channel that displays selective permeability to calcium ions with a transient length of activation. Burst firing refers to periods of rapid neural spiking followed by quiescent, silent, periods. Sleep spindles are bursts of oscillatory brain activity visible on an EEG that occurs during non-rapid eye movement stage 2, or NREM-2, sleep, during which no eye movement occurs, and dreaming is very rare.) The scientists presented both in vivo and in vitro evidence that sleep spindles are generated normally in the absence of T-type channels and burst firing (periods of rapid neural spiking followed by quiescent, silent, periods) in thalamocortical neurons. Moreover, their results show what they describe as a potentially important role of tonic (constant) firing in this rhythm generation. They conclude that future studies should be aimed at investigating the detailed mechanism through which each type of thalamocortical oscillation is generated.
Dr. Hee-Sup Shin and Prof. Eunji Cheong discussed the paper that they recently published in Proceedings of the National Academy of Sciences. “The previous theory implicated thalamocortical TC burst firing in all sleep waves which appear in different sleep stages,” Cheong tells Medical Xpress. “However, we’ve long questioned the extent to which thalamocortical T-type Ca2+ channels and the resulting burst firing contribute to the heterogeneity of thalamocortical oscillations during non-rapid eye movement sleep consisting of multiple brain waves.” A T-type Ca2+channel is a type of voltage-gated ion channel which displays selective permeability to calcium ions, in this case with a transient length of activation.
Shin notes that the scientists faced a number of issues in designing and interpreting the results of the in vivo and in vitro experiments to test their hypothesis. “Since we observed the quite intact sleep spindles in CaV3.1 knockout mice, we tried to figure out how the sleep spindles are generated in the absence of a thalamocortical burst.” (A gene knockout, or KO, is a genetic technique in which one of an organism’s genes is made inoperative to learn about its function from the difference between the knockout organism and normal individuals. CaV3.1 is a T-type calcium channel found in neurons, cells that have pacemaker activity.) “The issues were if the spindles are generated within the thalamocortical circuit as previously known, and how thalamocortical neurons generate spikes during spindles in the presence or absence of a thalamocortical burst.” All of the researchers’ the experiments were designed to investigate these questions.
"The purpose of in vitro thalamocortical-thalamic reticular nucleus,” or TC-TRN, “network oscillations was to show if thalamocortical oscillations observed in CaV3.1 knockout mice could be generated either within an intrathalamic network or if they were cortical driven oscillations,” Cheong points out. “Another difference between in vivo and in vitro networks is that compared to in vivo network all the afferent inputs into TC or TRN are not intact in an in vitro TC-TRN network.” The results showed that spindle-like oscillations were generated even in the absence of cortex.
The study shows that these differences also relate to In vivo data suggesting that TRN neurons are spindle pacemakers. “There have been debates on the leading role of TRN versus cortex in pacing the sleep spindles. In an in vitro TC-TRN network, both the afferent inputs and corticothalamic inputs onto TC neurons are not intact,” Shin explains. “Therefore, major inputs onto TC neurons in those experiments come from TRN neurons. The generation of intrathalamic oscillations under this condition indicates that the reciprocal connection between TRN and TC could generate the oscillations, which adds weight to the TRN neurons as spindle pacemakers. The generation of CaV3.1 knockout mice which lack T-type Ca2+ channels in TC neurons was the key to address this issue.”
Cheong emphasizes that the study’s major findings call into question the essential role of low-threshold burst firings in thalamocortical neurons. “It’s noteworthy that tonic spikes were more abundant than burst spikes during spindles even in wild Type thalamocortical neurons – not only in CaV3.1-/- TC neurons – whereas no difference in tonic and burst spike frequency was seen during non-spindle periods. Moreover,” he continues, “the tonic spike frequency increases significantly during cortical spindle events compared to non-spindle periods even in wild-type TC neurons. This is clearly different from that seen for burst spike frequency in wild-type TC neurons, which occurred with almost equal incidence during both the spindle and non-spindle periods.” Therefore, Cheong points out, the scientists concluded that TC burst firing is not required for the generation in spindle generation.
The researchers also found that the peak frequency of sleep spindles was not different between wild and CaV3.1 KO mice, which suggested that TC spikes are not critical in determining the spindle frequency. However, Shin notes, the question of what drives TC neurons to fire during spindles remains to be further investigated, although they think that TC firing during spindles indicates that the TC-TRN network is not as simple as previously believed.
Moving forward, Cheong tells Medical Xpress, the researchers would like to further investigate the firing pattern of TC neurons during natural NREM sleep, including spindle, delta and slow waves. and also elucidate the detailed ensemble behavior of neuron within thalamocortical network during sleep. Moreover, TC burst firing has long been implicated in both physiological thalamocortical oscillations during both sleep and pathological thalamocortical oscillations, such as spike-wave-discharges appearing in absence epilepsy. “Our current study clearly showed that TC burst are not essential for sleep spindles, which would be helpful information to develop the anti-epileptic agents,” Shin concludes.
Synaptic mechanisms of brain waves
Team at IST Austria examines synaptic mechanisms of rhythmic brain waves • Achievement possible through custom-design tools developed in collaboration with the institute’s Miba machine shop
How information is processed and encoded in the brain is a central question in neuroscience, as it is essential for high cognitive function such as learning and memory. Theta-gamma oscillations are “brain waves” observed in the hippocampus of behaving rats, a brain region involved in learning and memory. In rodents, theta-gamma oscillations are associated with information processing during exploration and spatial navigation. However, the underlying synaptic mechanisms have so far remained unclear. In research published this week in the journal Neuron, postdoc Alejandro Pernía-Andrade and Professor Peter Jonas, both at the Institute of Science and Technology Austria (IST Austria), discovered the synaptic mechanisms underlying oscillations at the dentate gyrus (main entrance of the hippocampus). Furthermore, the researchers suggest a role for these oscillations in the coding of information by the dentate gyrus principal neurons. Thus, these findings contribute to a better understanding of how information is processed in the brain.
Brain oscillations are, in fact, rhythmic changes in voltage in the extracellular space, referred to as electrical brain signals associated with the processing of information. These electrical signals are similar to those seen in electro-encephalographic recordings (EEG) in humans. Pernía-Andrade and Jonas observed these oscillations in a brain region called the hippocampus in behaving rats, and recorded oscillations occurring in this area using extracellular probes. To understand how oscillations are generated and which synaptic events trigger these oscillations, the researchers looked at synaptic transmission in granule cells (principal cells at the main entrance of the hippocampus) from both the extracellular (oscillations) and the intracellular perspectives (synaptic currents and neuronal firing), and then correlated the two. They discovered that excitatory and inhibitory synaptic signals contributed to different frequencies of oscillations, with excitation from the entorhinal cortex generating theta oscillations and inhibition by local dentate gyrus interneurons generating gamma oscillations. Together, excitation and inhibition provide the rhythmic signals of oscillations. It has been speculated that oscillations may help the dentate gyrus to encode information by acting as reference signals in temporal coding. Pernía-Andrade and Jonas now show that granule cell neurons send signals only at specific times in the cycle of oscillations. This so-called “phase locking” is necessary if oscillations are to function as reference signals in temporal coding.
The precise, high-resolution recording from granule cells necessary for these discoveries was possible only through technological innovations by Pernía-Andrade and Jonas, as previously no equipment was available to record synaptic signals in active rats in such high resolution. They are the result of a collaboration with the Miba machine shop, IST Austria’s electrical and mechanical SSU (Scientific Service Unit). Adapting commercially available equipment and custom-designing tools, Pernía-Andrade, Jonas and Todor Asenov, manager of the Miba machine shop, produced the first tools for precise biophysical analysis in active rats. This research is therefore not only a scientific advance but also represents a significant technological and conceptual progress in the quest to understand neuronal behavior under natural conditions.
(Source: ist.ac.at)
How Our Sense of Touch is a Lot Like the Way We Hear
Sliman Bensmaia, PhD, assistant professor of organismal biology and anatomy at the University of Chicago, studies the neural basis of tactile perception, or how our hands convey this information to the brain. In a new study published in the Journal of Neuroscience, he and his colleagues found that the timing and frequency of vibrations produced in the skin when you run your hands along a surface, like searching a wall for a light switch, play an important role in how we use our sense of touch to gather information about the objects and surfaces around us.
The sense of touch has traditionally been thought of in spatial terms, i.e. receptors in the skin are spread out across a grid of sorts, and when you touch something this grid of receptors transmits information about the surface to your brain. In their new study, Bensmaia, two former undergraduates, and a postdoctoral scholar in his lab—Matthew Best, Emily Mackevicius and Hannes Saal—found that the skin is also highly sensitive to vibrations, and that these vibrations produce corresponding oscillations in the afferents, or nerves, that carry information from the receptors to the brain. The precise timing and frequency of these neural responses convey specific messages about texture to the brain, much like the frequency of vibrations on the eardrum conveys information about sound.
Neurons communicate through electrical bits, similar to the digital ones and zeros used by computers. But, Bensmaia said, “One of the big questions in neuroscience is whether it’s just the number of bits that matters, or if the specific sequence of bits in time also plays a role. What we show in this paper is that the sequence of bits in time does matter, and in fact for some of the skin receptors, the timing matters with millisecond precision.”
Researchers have known for years that these afferents respond to skin vibrations, but they studied their responses using so-called sinusoidal waves, which are smooth, repetitive patterns. These perfectly uniform vibrations can be produced in a lab, but the kinds of vibrations produced in the skin by touching surfaces in the real world are messy and erratic.
Naturally, our brain activity waxes and wanes. When listening, this oscillation synchronizes to the sounds we are hearing. Researchers at the Max Planck Institute for Human Cognitive and Brain Sciences have found that this influences the way we listen. Hearing abilities also oscillate and depend on the exact timing of one’s brain rhythms. This discovery that sound, brain, and behaviour are so intimately coupled will help us to learn more about listening abilities in hearing loss.
Inside the unconscious brain
A new study from MIT and Massachusetts General Hospital (MGH) reveals, for the first time, what happens inside the brain as patients lose consciousness during anesthesia.
By monitoring brain activity as patients were given a common anesthetic, the researchers were able to identify a distinctive brain activity pattern that marked the loss of consciousness. This pattern, characterized by very slow oscillation, corresponds to a breakdown of communication between different brain regions, each of which experiences short bursts of activity interrupted by longer silences.
“Within a small area, things can look pretty normal, but because of this periodic silencing, everything gets interrupted every few hundred milliseconds, and that prevents any communication,” says Laura Lewis, a graduate student in MIT’s Department of Brain and Cognitive Sciences (BCS) and one of the lead authors of a paper describing the findings in the Proceedings of the National Academy of Sciences this week.
This pattern may help anesthesiologists to better monitor patients as they receive anesthesia, preventing rare cases where patients awaken during surgery or stop breathing after excessive doses of anesthesia drugs.
Brain waves reveal video game aptitude
Scientists report that they can predict who will improve most on an unfamiliar video game by looking at their brain waves. They describe their findings in a paper in the journal Psychophysiology.
The researchers used electroencephalography (EEG) to peek at electrical activity in the brains of 39 study subjects before they trained on Space Fortress, a video game developed for cognitive research. The subjects whose brain waves oscillated most powerfully in the alpha spectrum (about 10 times per second, or 10 hertz) when measured at the front of the head tended to learn at a faster rate than those whose brain waves oscillated with less power, the researchers found. None of the subjects were daily video game players.
The EEG signal was a robust predictor of improvement on the game, said University of Illinois postdoctoral researcher and Beckman Fellow Kyle Mathewson, who led the research with psychology professors and Beckman Institute faculty members Monica Fabiani and Gabriele Gratton.
“By measuring your brain waves the very first time you play the game, we can predict how fast you’ll learn over the next month,” Mathewson said. The EEG results predicted about half of the difference in learning speeds between study subjects, he said.
Alpha Waves Close Your Mind for Distraction, but Not Continuously, Research Suggests
Alpha waves were long ignored, but gained interest of brain researchers recently. Electrical activity of groups of brain cells results in brain waves with different amplitudes. The so-called alpha wave, a slow brain wave with a cycle of 100 milliseconds, seems to play a key role in suppressing irrelevant brain activity. The current hypothesis is that this alpha wave is associated with pulses of inhibition (every 100 ms) in the brain.
Mathilde Bonnefond and Ole Jensen (Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen) discovered that when distracting information can be anticipated in time there is an increase of the power of this alpha wave just before the distracter. Furthermore, the brain is able to precisely control the alpha wave so that the pulse of inhibition is maximal when the distracter appears. Indeed, between pulses of inhibition, there is still a window where the brain is excitable.
'It is like briefly opening a door to look what's happening outside. This enables us to detect an unexpected but important or dangerous event. But to avoid to be distracted by completely irrelevant information, it is better if the inhibition is active when a distracter is presented. It could be seen as a mechanism slamming the door of the brain on intruders'. The results are published by the scientific journal Current Biology at October 4.