Silent stroke can cause Parkinson’s disease

Scientists at The University of Manchester have for the first time identified why a patient who appears outwardly healthy may develop Parkinson’s disease.

Whilst conditions such as a severe stroke have been linked to the disease, for many sufferers the tremors and other symptoms of Parkinson’s disease can appear to come out of the blue. Researchers at the university’s Faculty of Life Sciences have now discovered that a small stroke, also known as a silent stroke, can cause Parkinson’s disease. Their findings have been published in the journal “Brain Behaviour and Immunity”.

Unlike a severe stroke, a silent stroke can show no outward symptoms of having taken place. It happens when a blood vessel in the brain is blocked for only a very short amount of time and often a patient won’t know they have suffered from one. However, it now appears one of the lasting effects of a silent stroke can be the death of dopaminergic neurons in the substantia nigra in the brain, which is an important region for movement coordination.

Dr. Emmanuel Pinteaux led the research: “At the moment we don’t know why dopaminergic neurons start to die in the brain and therefore why people get Parkinson’s disease. There have been suggestions that oxidative stress and aging are responsible. What we wanted to do in our study was to look at what happens in the brain away from the immediate area where a silent stroke has occurred and whether that could lead to damage that might result in Parkinson’s disease.”

The team induced a mild stroke similar to a silent stroke in the striatum area of the brain in mice. They found there was inflammation and brain damage in the striatum following the stroke, which they had expected. What the researchers didn’t expect was the impact on another area of the brain, the substantia nigra. When they analysed the substantia nigra they recorded a rapid loss of Substance P (a key chemical involved in its functions) as well as inflammation.

The team then analysed changes in the brain six days after the mild stroke and found neurodegeneration in the substantia nigra. Dopaminergic neurones had been killed.

Talking about the findings Dr Pinteaux said: “It is well known that inflammation following a stroke can be very damaging to the brain. But what we didn’t fully appreciate was the impact on areas of the brain away from the location of the stroke. Our work identifying that a silent stroke can lead to Parkinson’s disease shows it is more important than ever to ensure stroke patients have swift access to anti-inflammatory medication. These drugs could potentially either delay or stop the on-set of Parkinson’s disease.”

Dr Pinteaux continued: “What our findings also point to is the importance of maintaining a healthy lifestyle. There are already guidelines about exercise and healthy eating to help reduce the risk of having a stroke and our research suggests that a healthy lifestyle can be applied to Parkinson’s disease as well.”

Following the publication of these findings, Dr Pinteaux hopes to set up a clinical investigation on people who have had a silent stroke to assess dopaminergic neuron degeneration. In the meantime he will be working closely will colleagues at The University of Manchester to better understand the mechanisms of inflammation in the substantia nigra. 

Even the Smallest Possible Stroke Can Damage Brain Tissue and Impair Cognitive Function

Blocking a single tiny blood vessel in the brain can harm neural tissue and even alter behavior, a new study from the University of California, San Diego has shown. But these consequences can be mitigated by a drug already in use, suggesting treatment that could slow the progress of dementia associated with cumulative damage to miniscule blood vessels that feed brain cells. The team reports their results in the December 16 advance online edition of Nature Neuroscience.

"The brain is incredibly dense with vasculature. It was surprising that blocking one small vessel could have a discernable impact on the behavior of a rat," said Andy Y. Shih, lead author of the paper who completed this work as a postdoctoral fellow in physics at UC San Diego. Shih is now an assistant professor at the Medical University of South Carolina.

Working with rats, Shih and colleagues used laser light to clot blood at precise points within small blood vessels that dive from the surface of the brain to penetrate neural tissue. When they looked at the brains up to a week later, they saw tiny holes reminiscent of the widespread damage often seen when the brains of patients with dementia are examined as a part of an autopsy.

These micro-lesions are too small to be detected with conventional MRI scans, which have a resolution of about a millimeter. Nearly two dozen of these small vessels enter the brain from a square millimeter area of the surface of the brain.

"It’s controversial whether that sort of damage has consequences, although the tide of evidence has been growing as human diagnostics improve," said David Kleinfeld, professor of physics and neurobiology, who leads the research group.

To see whether such minute damage could change behavior, the scientists trained thirsty rats to leap from one platform to another in the dark to get water.

The rats readily jump if they can reach the second platform with a paw or their snout, or stretch farther to touch it with their whiskers. Many rats can be trained to rely on a single whisker if the others are clipped, but if they can’t feel the far platform, they won’t budge.

"The whiskers line up in rows and each one is linked to a specific spot in the brain," Shih said. "By training them to use just one whisker, we were able to distill a behavior down to a very small part of the brain."

When Shih blocked single microvessels feeding a column of brain cells that respond to signals from the remaining whisker, the rats still crossed to the far platform when the gap was small. But when it widened beyond the reach of their snouts, they quit.

The FDA-approved drug memantine, prescribed to slow one aspect of memory decline associated with Alzheimer’s disease, ameliorated these effects. Rats that received the drug jumped whisker-wide gaps, and their brains showed fewer signs of damage.

"This data shows us, for the first time, that even a tiny stroke can lead to disability," said Patrick D. Lyden, a co-author of the study and chair of the department of neurology at Cedars-Sinai Medical Center in Los Angeles. "I am afraid that tiny strokes in our patients contribute—over the long term—to illness such as dementia and Alzheimer’s disease," he said, adding that "better tools will be required to tell whether human patients suffer memory effects from the smallest strokes."

“We used powerful tools from biological physics, many developed in Kleinfeld’s laboratory at UC San Diego, to link stroke to dementia on the unprecedented small scale of single vessels and cells,” Shih said. “At my new position at MUSC, I plan to work on ways to improve the detection of micro-lesions in human patients with MRI. This way clinicians may be able to diagnose and treat dementia earlier.”

Study Shows Working Memory Is Driven By Prefrontal Cortex And Dopamine

One of the unique features of the human mind is its ability re-prioritize its goals and priorities as situations change and new information arises. This happens when you cancel a planned cruise because you need the money to repair your broke-down car, or when you interrupt your morning jog because your cell phone is ringing in your pocket.

In a new study published in the Proceedings of the National Academy of Sciences (PNAS), researchers from Princeton University say that they have discovered the mechanisms that control how our brains use new information to modify our existing priorities.

The team of researchers at Princeton’s Neuroscience Institute (PNI) used functional magnetic resonance imaging (fMRI) to scan subjects and find out where and how the human brain reprioritizes goals. Unsurprisingly, they found that the shifting of goals takes place in the prefrontal cortex, a region of the brain which is known to be associated with a variety of higher-level behaviors. They also observed that the powerful neurotransmitter dopamine – also known as the “pleasure chemical” – appears to play a critical role in this process.

Using a harmless magnetic pulse, the scientists interrupted activity in the prefrontal cortex of the participants while they were playing games and found they were unable to switch to a different task in the game.

“We have found a fundamental mechanism that contributes to the brain’s ability to concentrate on one task and then flexibly switch to another task,” explained Jonathan Cohen, co-director of PNI and the university’s Robert Bendheim and Lynn Bendheim Thoman Professor in Neuroscience.

“Impairments in this system are central to many critical disorders of cognitive function such as those observed in schizophrenia and obsessive-compulsive disorder.”

Previous research had already demonstrated that when the brain uses new information to modify its goals or behaviors, this information is temporarily filed away into the brain’s working memory, a type of short-term memory storage. Until now, however, scientists have not understood the mechanisms controlling how this information is updated.

Why Music Moves Us

Universal emotions like anger, sadness and happiness are expressed nearly the same in both music and movement across cultures, according to new research.

The researchers found that when Dartmouth undergraduates and members of a remote Cambodian hill tribe were asked to use sliding bars to adjust traits such as the speed, pitch, or regularity of music, they used the same types of characteristics to express primal emotions. What’s more, the same types of patterns were used to express the same emotions in animations of movement in both cultures.

"The kinds of dynamics you find in movement, you find also in music and they’re used in the same way to provide the same kind of meaning," said study co-author Thalia Wheatley, a neuroscientist at Dartmouth University.

The findings suggest music’s intense power may lie in the fact it is processed by ancient brain circuitry used to read emotion in our movement.

"The study suggests why music is so fundamental and engaging for us," said Jonathan Schooler, a professor of brain and psychological sciences at the University of California at Santa Barbara, who was not involved in the study. "It takes advantage of some very, very basic and, in some sense, primitive systems that understand how motion relates to emotion."

Universal emotions

Why people love music has been an enduring mystery. Scientists have found that animals like different music than humans and that brain regions stimulated by food, sex and love also light up when we listen to music. Musicians even read emotions better than nonmusicians.

Past studies showed that the same brain areas were activated when people read emotion in both music and movement. That made Wheatley wonder how the two were connected.

To find out, Wheatley and her colleagues asked 50 Dartmouth undergraduates to manipulate five slider bars to change characteristics of an animated bouncy ball to make it look happy, sad, angry, peaceful or scared.

"We just say ‘Make Mr. Ball look angry or make Mr. Ball look happy,’" she told LiveScience.

To create different emotions in “Mr. Ball,” the students could use the slider bars to affect how often the ball bounced, how often it made big bounces, whether it went up or down more often and how smoothly it moved.

Another 50 students could use similar slider bars to adjust the pitch trajectory, tempo, consonance (repetition), musical jumps and jitteriness of music to capture those same emotions.

The students tended to put the slider bars in roughly the same positions whether they were creating angry music or angry moving balls.

To see if these trends held across cultures, Wheatley’s team traveled to the remote highlands of Cambodia and asked about 85 members of the Kreung tribe to perform the same task. Kreung music sounds radically different from Western music, with gongs and an instrument called a mem that sounds a bit like an insect buzzing, Wheatley said. None of the tribes’ people had any exposure to Western music or media, she added.

Interestingly, the Kreung tended to put the slider bars in roughly the same positions as Americans did to capture different emotions, and the position of the sliders was very similar for both music and emotions.

The findings suggest that music taps into the brain networks and regions that we use to understand emotion in people’s movements. That may explain why music has such power to move us — it’s activating deep-seated brain regions that are used to process emotion, Wheatley said.

"Emotion is the same thing no matter whether it’s coming in through our eyes or ears," she said.

Brain imaging identifies bipolar risk

Researchers from the Black Dog Institute and University of NSW have used brain imaging technology to show that young people with a known genetic risk of bipolar but no clinical signs of the condition have clear and quantifiable differences in brain activity when compared to controls.

“We found that the young people who had a parent or sibling with bipolar disorder had reduced brain responses to emotive faces, particularly a fearful face. This is an extremely promising breakthrough,” says study leader Professor Philip Mitchell.

Affecting around 1 in 75 Australians, bipolar disorder involves extreme and often unpredictable fluctuations in mood. The mood swings and associated behaviours such as disinhibited behaviour, aggression and severe depression, have a significant impact on day-to-day life, careers and relationships. Bipolar has the highest suicide rate of all psychiatric disorders.

“We know that bipolar is primarily a biological illness with a strong genetic influence but triggers are yet to be understood. Being able to identify young people at risk will enable implementation of early intervention programs, giving them the best chance for a long and happy life,” says Prof Mitchell.

Researchers used functional MRI to visualise brain activity when participants were shown pictures of happy, fearful or calm (neutral) human faces. Results showed that those with a genetic risk of bipolar displayed significantly reduced brain activity in a specific part of the brain known to regulate emotional responses.

“Our results show that bipolar disorder may be linked to a dysfunction in emotional regulation and this is something we will continue to explore,” Professor Mitchell said.

“And we now have an extremely promising method of identifying children and young people at risk of bipolar disorder.”

 “We expect that early identification will significantly improve outcomes for people that go on to develop bipolar disorder, and possibly even prevent onset in some people.”

Results are published this week in Biological Psychiatry and come from the NHMRC-funded ‘Kids and Sibs study’, the biggest research study in the world focusing on genetic and environmental aspects of bipolar disorder. Based at the Black Dog Institute, the trial is still recruiting.

A More Human Artificial Brain

Staying on task

Its full name is the Semantic Pointer Architecture Unified Network, but Spaun sounds way more epic. It’s the latest version of a techno brain, the creation of a Canadian research team at the University of Waterloo.

So what makes Spaun different from a mindboggingly smart artificial brain like IBM’s Watson? Put simply, Watson is designed to work like a supremely powerful search engine, digging through an enormous amount of data at breakneck speed and using complex algorithms to derive an answer. It doesn’t really care about how the process works; it’s mainly about mastering information retrieval.

But Spaun tries to actually mimic the human brain’s behavior and does so by performing a series of tasks, all different from each other. It’s a computer model that can not only recognize numbers with its virtual eye and remember them, but also can manipulate a robotic arm to write them down.

Spaun’s “brain” is divided into two parts, loosely based on our cerebral cortex and basil ganglia and its simulated 2.5 million neurons–our brains have 100 billion–are designed to mimic how researchers think those two parts of the brain interact.

Say, for instance, that its “eye” sees a series of numbers. The artificial neurons take that visual data and route it into the cortex where Spaun uses it to perform a number of different tasks, such as counting, copying the figures, or solving number puzzles.

Soon it will be forgetting birthdays

But there’s been an interesting twist to Spaun’s behavior. As Francie Diep wrote in Tech News Daily, it became more human than its creators expected.

Ask it a question and it doesn’t answer immediately. No, it pauses slightly, about as long as a human might. And if you give Spaun a long list of numbers to remember, it has an easier time recalling the ones it received first and last, but struggles a bit to remember the ones in the middle.

“There are some fairly subtle details of human behavior that the model does capture,” says Chris Eliasmith, Spaun’s chief inventor. “It’s definitely not on the same scale. But it gives a flavor of a lot of different things brains can do.”

Brain drains

The fact that Spaun can move from one task to another brings us one step closer to being able to understand how our brains are able to shift so effortlessly from reading a note to memorizing a phone number to telling our hand to open a door.

And that could help scientists equip robots with the ability to be more flexible thinkers, to adjust on the fly. Also, because Spaun operates more like a human brain, researchers could use it to run health experiments that they couldn’t do on humans.

Recently, for instance, Eliasmith ran a test in which he killed off the neurons in a brain model at the same rate that neurons die in people as they age. He wanted to see how the loss of neurons affected the model’s performance on an intelligence test.

One thing Eliasmith hasn’t been able to do is to get Spaun to recognize if it’s doing a good or a bad job. He’s working on it.

Aerobic exercise boosts brain power in elderly

Evidence for the importance of physical activity in keeping and potentially improving cognitive function throughout life was found in a literature review in Psychonomic Bulletin & Review by Hayley Guiney and Liana Machado from the University of Otago, New Zealand.

• Cognitive functions such as task switching, selective attention, and working memory appear to benefit from aerobic exercise. Studies in older adults reviewed by the authors consistently found that fitter individuals scored better in mental tests than their unfit peers.
  
  
• Scores in mental tests improved in participants who were assigned to an aerobic exercise regimen compared to those assigned to stretch and tone classes.
  
  
• Exercise has been found to positively affect mental tasks relating to activities such as driving, an activity where age is often seen as a limiting factor.
  
  
• MRI studies of aging have shown that, as compared with unfit, highly fit older adults exhibit less age-related atrophy in the prefrontal and temporal cortices; preserved neural tracts connecting the prefrontal cortex to other regions of the brain; superior white matter integrity in the corpus callosum; greater gray matter density in the frontal, temporal, and parietal cortices; and greater hippocampal volumes.
  
  
• Physically active older adults have both higher circulating neurotrophin levels and gray matter volumes in the prefrontal and cingulate cortex.
  
  
• These results were not replicated in children or young adults, except for memory tasks. Both the updating of working memory and the volume of information which could be held was also better in young fitter individuals or those put on an aerobic exercise regime. “Although the evidence to date supports a wider range of executive functions benefiting from regular exercise in older adults, the relative lack of supportive evidence in young adults and children may, in part, reflect a poverty of studies, especially controlled trials, in these age groups,” the authors suggest.

Woman With Quadriplegia Feeds Herself Chocolate Using Mind-Controlled Robot Arm

In a study published in the online version of The Lancet, the researchers described the brain-computer interface (BCI) technology and training programs that allowed Ms. Scheuermann, 53, of Whitehall Borough in Pittsburgh, Pa. to intentionally move an arm, turn and bend a wrist, and close a hand for the first time in nine years.

Less than a year after she told the research team, “I’m going to feed myself chocolate before this is over,” Ms. Scheuermann savored its taste and announced as they applauded her feat, “One small nibble for a woman, one giant bite for BCI.”

“This is a spectacular leap toward greater function and independence for people who are unable to move their own arms,” agreed senior investigator Andrew B. Schwartz, Ph.D., professor, Department of Neurobiology, Pitt School of Medicine. “This technology, which interprets brain signals to guide a robot arm, has enormous potential that we are continuing to explore. Our study has shown us that it is technically feasible to restore ability; the participants have told us that BCI gives them hope for the future.”

In 1996, Ms. Scheuermann was a 36-year-old mother of two young children, running a successful business planning parties with murder-mystery themes and living in California when one day she noticed her legs seemed to drag behind her. Within two years, her legs and arms progressively weakened to the point that she required a wheelchair, as well as an attendant to assist her with dressing, eating, bathing and other day-to-day activities. After returning home to Pittsburgh in 1998 for support from her extended family, she was diagnosed with spinocerebellar degeneration, in which the connections between the brain and muscles slowly, and inexplicably, deteriorate.