A different drummer: Neural rhythms drive physical movement

The 19th century mathematician Joseph Fourier showed that two rhythms could be summed to produce a third rhythm. Researchers at Stanford have shown that this principle is behind the brain activity that produces arm movements. Credit: Mark Churchland, Stanford School of Engineering

Unlike their visual cousins, the neurons that control movement are not a predictable bunch. Scientists working to decode how such neurons convey information to muscles have been stymied when trying to establish a one-to-one relationship between a neuron's behavior and external factors such as muscle activity or movement velocity.

In an article published online June 3rd by the journal Nature, a team of electrical engineers and neuroscientists working at Stanford University propose a new theory of the brain activity behind arm movements. Their theory is a significant departure from existing understanding and helps to explain, in relatively simple and elegant terms, some of the more perplexing aspects of the activity of neurons in motor cortex.

In their paper, electrical engineering Associate Professor Krishna Shenoy and post-doctoral researchers Mark Churchland, now a professor at Columbia, and John Cunningham of Cambridge University, now a professor at Washington University in Saint Louis, have shown that the brain activity controlling arm movement does not encode external spatial information—such as direction, distance and speed—but is instead rhythmic in nature.

Understanding the brain

Neuroscientists have long known that the neurons responsible for vision encode specific, external-world information—the parameters of sight. It had been theorized and widely suggested that motor cortex neurons function similarly, conveying specifics of movement such as direction, distance and speed, in the same way the visual cortex records color, intensity and form.

"Visual neurons encode things in the world. They are a map, a representation," said Churchland, who is first author of the paper. "It's not a leap to imagine that neurons in the motor cortex should behave like neurons in the visual cortex, relating in a faithful way to external parameters, but things aren't so concrete for movement."

Scientists have disagreed about which movement parameters are being represented by individual neurons. They could not look at a particular neuron firing in the motor cortex and determine with confidence what information it was encoding.

"Many experiments have sought such lawfulness and yet none have found it. Our findings indicate an alternative principle is at play," said co-first author Cunningham.

"Our main finding is that the motor cortex is a flexible pattern generator, and sends rhythmic signals down the spinal cord," said Churchland.

Engine of movement

To employ an automotive analogy, the motor cortex is not the steering wheel, odometer or speedometer representing real-world information. It is more like an engine, comprised of parts whose activities appear complicated in isolation, but which cooperate in a lawful way as a whole to generate motion.

"If you saw a piston or a spark plug by itself, would you be able to explain how it makes a car move?" asked Cunningham rhetorically. "Motor-cortex neurons are like that, too, understandable only in the context of the whole."

In a series of striking graphs, the Stanford team plotted the signals from individual neurons in the motor-cortex as monkeys completed a series of reaches. The reaching motions are shown by the starburst patterns at the top left of each graph. The neuronal patterns are then plotted atop one another for the entire series of reaches, clearly establishing the rhythmic nature of the brain activity. Credit: Mark Churchland, Stanford School of Engineering

In monitoring electrical brain activity of motor-cortex neurons, researchers found that they typically exhibit a brief oscillatory response. These responses are not independent from neuron to neuron. Instead, the entire neural population oscillates as one in a beautiful and lawfully coordinated way.

The electrical signal that drives a given movement is therefore an amalgam – a summation – of the rhythms of all the motor neurons firing at a given moment.

"Under this new way of looking at things, the inscrutable becomes predictable," said Churchland. "Each neuron behaves like a player in a band. When the rhythms of all the players are summed over the whole band, a cascade of fluid and accurate motion results."

Dr. Daofen Chen, Program Director, Systems and Cognitive Neuroscience at the National Institute of Neurological Disorders and Stroke at the National Institutes of Health, said Shenoy and team are working at the cutting edge of the field. "In trying to find the basic response properties of the motor cortex, Dr. Shenoy and his colleagues are searching for the holy grail of neuroscience," said Dr. Chen. "His team has been consistent in tackling important but tough questions, often in thought-provoking ways and in ambitious proposals. NIH is proud to support this kind of pioneering and transformative research."

Precedents in nature

In the new model, a few relatively simple rhythms explain neural features that had confounded science earlier.

"Many of the most-baffling aspects of motor-cortex neurons seem natural and straightforward in light of this model," said Cunnigham.

The team studied non-rhythmic reaching movements, which made the presence of rhythmic neural activity a surprise even though, the team notes, rhythmic neural activity has a long precedence in nature. Such rhythms are present in the swimming motion of leeches and the gait of a walking monkey, for instance.

"The brain has had an evolutionary goal to drive movements that help us survive. The primary motor cortex is key to these functions. The patterns of activity it displays presumably derive from evolutionarily older rhythmic motions such as swimming and walking. Rhythm is a basic building block of movement," explained Churchland.

Reaching for the grail

To test their hypothesis, the engineers studied the brain activity of monkeys reaching to touch a target. According to the researchers, experiments show this 'underlying rhythm' strategy works very well to explain both brain and muscle activity. In their reaching studies, the pattern of shoulder-muscle behavior could always be described by the sum of two underlying rhythms.

"Say you're throwing a ball. Beneath it all is a pattern. Maybe your shoulder muscle contracts, relaxes slightly, contracts again, and then relaxes completely, all in short order," explained Churchland. "That activity may not be exactly rhythmic, but it can be created by adding together two or three other rhythms. Our data argue that this may be how the brain solves the problem of creating the pattern of movement."

"Finding these brain rhythms surprised us a bit, as the reaches themselves were not rhythmic. In fact, they were decidedly arrhythmic, and yet underlying it all were these unmistakable patterns," said Churchland.

"This research builds on a strong theoretical framework and adds to growing evidence that rhythmic activity is important for many fundamental brain functions," said Yuan Liu of the National Institute of Neurological Disorders and Stroke, NIH. "Further research in this area may help us devise more effective technology for controlling prosthetic limbs." Liu is the co-lead of the NIH-NSF Collaborative Research in Computational Neuroscience program.

"In this model, the seemingly complex system that is the motor cortex can now be at least partially understood in more straightforward terms. The motor cortex is an engine of movement that obeys lawful dynamics," said Shenoy.

Stanford post-doctoral fellow Matthew Kaufman, bioengineering PhD student and medical science training program student Paul Nuyujukian, electrical engineering graduate student Justin Foster, and electrical engineering consulting assistant professor and Palo Alto Medical Foundation neurosurgeon Stephen Ryu were also authors on this paper.

Provided by Stanford University

"A different drummer: Neural rhythms drive physical movement." June 3rd, 2012.http://medicalxpress.com/news/2012-06-drummer-neural-rhythms-physical-movement.html

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Robert Karl Stonjek

Brain scans prove Freud right: Guilt plays key role in depression

Scientists have shown that the brains of people with depression respond differently to feelings of guilt – even after their symptoms have subsided.

University of Manchester researchers found that the brain scans of people with a history of depression differed in the regions associated with guilt and knowledge of socially acceptable behaviour from individuals who never get depressed.

The study – published in the journal Archives of General Psychiatry – provides the first evidence of brain mechanisms to explain Freud's classical observation that exaggerated guilt and self-blame are key to understanding depression.

Lead researcher Dr Roland Zahn, from the University's School of Psychological Sciences, said: "Our research provides the first brain mechanism that could explain the classical observation by Freud that depression is distinguished from normal sadness by proneness to exaggerated feelings of guilt or self-blame.

"For the first time, we chart the regions of the brain that interact to link detailed knowledge about socially appropriate behaviour – the anterior temporal lobe – with feelings of guilt – the subgenual region of the brain – in people who are prone to depression."

The study used functional magnetic resonance imaging (fMRI) to scan the brains of a group of people after remission from major depression for more than a year, and a control group who have never had depression. Both groups were asked to imagine acting badly, for example being 'stingy' or 'bossy' towards their best friends. They then reported their feelings to the research team.

"The scans revealed that the people with a history of depression did not 'couple' the brain regions associated with guilt and knowledge of appropriate behaviour together as strongly as the never depressed control group do," said Dr Zahn, a MRC Clinician Scientist Fellow.

"Interestingly, this 'decoupling' only occurs when people prone to depression feel guilty or blame themselves, but not when they feel angry or blame others. This could reflect a lack of access to details about what exactly was inappropriate about their behaviour when feeling guilty, thereby extending guilt to things they are not responsible for and feeling guilty for everything."

The research, part-funded by the Medical Research Council (MRC), is important because it reveals brain mechanisms underlying specific symptoms of depression that may explain why some people react to stress with depression rather than aggression.

The team is now investigating whether the results from the study can be used to predict depression risk after remission of a previous episode. If successful, this could provide the first fMRI marker of risk of future depression.

More information: 'Guilt-Selective Functional Disconnection of Anterior Temporal and Subgenual Cortices in Major Depressive Disorder,' by Sophie Green et al., Archives of General Psychiatry, 2012.

Provided by University of Manchester

"Brain scans prove Freud right: Guilt plays key role in depression." June 4th, 2012.http://medicalxpress.com/news/2012-06-brain-scans-freud-guilt-key.html

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Robert Karl Stonjek

Side effect: Crisis in Greece hits mental health

Greece is not feeling well. One in four men, and one in three women, has endured recent bouts of depression. As the grinding economic crisis continues to batter people's nerves, suicides and psychosomatic illness are both on the increase.

In April, a 77-year-old retiree, explaining in a note that he could no longer scrape by, went to a public square in the middle of Athens and put a bullet into his brain, a shot that echoed throughout the country.

While politicians and economists argue about how to pull Greece out of the quagmire of debt that has kneecapped its economy, there can be no doubt that the crisis -- once again threatening to eject the country from the eurozone towards an unknown fate -- is taking a devastating toil on the mental health of its people.

Compounding the emerging health care emergency is the fact that the state's ability to cope with it has been deeply eroded by the austerity measures and slashed budgets prescribed to cure the patient.

If you're going to have a nervous breakdown, in other words, Greece is not the best place to be.

"My patients are clearly much more on edge and stressed," said Dimitri, an osteopath in Athens with a varied clientele. "Their incomes are dropping. Their day-to-day relationships are fraying at the edges. Those who do have work are afraid of losing it, and show telltales signs of musculoskeletal tension."

Before the crisis really took hold, he added, half of his patients came for fine-tuning sessions, or for a minor realignment. "Now many arrive in a state of acute crisis. Their backs are blocked, or they can't even walk."

For Dimitri, there can be no doubt as to the culprit: the no-end-in-sight debt crisis that has plunged Greece deep into recession, ravaged its employment statistics and gutted social services.

The human body, he says, absorbs all these shocks like a spring.

"Often my patients don't know why they are in pain or unable to move, and tell me that they didn't lift anything heavy," he said. "Then, as we chat during the session, I find out that they're afraid of losing their jobs, or that a son's or daughter's salary has been cut in half, or that they can't pay the rent."

-- No way to keep a shred of dignity --

As officials vet new austerity measures and try to stave off further downgrades by credit agencies, the measureable impact of the crisis is getting inside the heads of Greeks.

Even if new elections later this month, called after a legislative vote on May 6 failed to produce a government, reverse course and reject the EU's austerity package, Greece is surely headed for more misery before things get any easier.

The numbers over the last year are sobering.

In the first half of 2011, more than a year after the economy began its dramatic slide, suicides in Greece shot up by 40 percent compared with the previous year. Almost daily, the media reports on someone who has put an end to it all because of financial burdens.

The old man who shot himself on April 4 in the middle of Syntagma Square -- site of many impassioned demonstrations against austerity measures -- clearly blamed his plight on the crisis.

"I can't see any other way to keep a shred of dignity and end my life without rummaging through garbage bins," the man wrote in a suicide note. Sick with cancer and living alone, he accused the state of depriving him of treatment after pensions were slashed, and compared the government in power to the one installed in 1941 by Nazi occupiers.

The man's fate seemed all the more shocking in a culture in which it is widely assumed that families can and will pick up the slack when the state falls short.

However, some of these numbers need to be put into perspective. Greece, like most other southern European countries, has a significantly lower suicide rate that northern nations. In 2009, before the crisis, the rate was three people for every 100,000 inhabitants, a third lower than the European average.

But there's no denying that Greece is in the doldrums.

According to health ministry statistics, a quarter of men and a third of women are depressed, double the European average for men, and nearly double for women. Calls to mental health hotlines also increased twofold in the first six months of 2011 compared with a year earlier.

"I don't sleep anymore," said 'Petros', who -- clearly embarrassed by his situation -- asked that his name be changed.

An importer/exporter of furniture with several stores in Athens, Petros said that over the last months he had been obliged to fire many staff, a first for his family-run enterprise. "And I'm going to have to cut the salaries of the ones that are left," he said, his voice brimming with emotion.

"I really wonder how people are going to get by after this summer, when most companies will have done the same," he added with creased brow.

-- State of war --

The crisis is not only making Greeks sick, it is making it harder for them to get treatment. Austerity measures have cut the national health budget by a devastating 25 percent since 2009.

"It's a state of war," said Yorgos Kalliabetsos, head of the pathology clinic at Volos Hospital in central Greece.

Doctors' salaries have been slashed by a quarter. Security staff are no longer paid at all. Nurses have become scarce, and shortages of medical supplies frequent. "My service has to take on 45 patients with 35 beds," Kalliabetsos lamented.

Since the uninsured have been left to their own devices, many now resort to desperate strategies.

"We have more and more patients who are inventing emergencies so they can be examined because they don't have any money for a regular consultation," explained Meropi Manteou, a lung specialist at Athens' enormous Sotiria Hospital. "We somehow manage to help the poorest patients that slip through the safety net, but for how much longer?"

An increase in poverty has brought in its wake an increase in diseases of the poor, notably tuberculosis.

The mental health picture is no less catastrophic. Several major psychiatric facilities have simply been shuttered. A third of the programmes to help addicts have also been shut down, which has led to a new wave of HIV infections.

Alexis, a 46-year-old journalist, has been treated since 2006 by Okana, an association that depends on the health ministry for street drug substitutes. He waited four years to get in the programme and feels lucky. "Most people who apply are dead by the time Okana calls them," he said.

The crisis has also encouraged the spread of a new street scourge called "sisa". Made from methamphetamines, the drug is ten times cheaper than heroin, but its effects are worse: blackened skin, sores all over the body, ultra-violent behaviour.

"One user stabbed another of my patients," recalled Emilios Katsoulakos, a psychiatrist. "There's no substitute we can prescribe for sisa."

Oddly, the economic downturn does seem to have had one salubrious impact: a decline in alcoholism. But that's probably only because new taxes on liquor -- another consequence of austerity -- make drowning one's sorrows too expensive.

(c) 2012 AFP

"Side effect: Crisis in Greece hits mental health." June 4th, 2012.http://medicalxpress.com/news/2012-06-side-effect-crisis-greece-mental.html

Posted by
Robert Karl Stonjek