Using electricity to synchronise brain waves boosts working memory

Brain activation patterns during stimulation

Scientists have uncovered a method for improving short-term working memory, by stimulating the brain with electricity to synchronise brain waves.

Researchers at Imperial College London found that applying a low voltage current can bring different areas of the brain in sync with one another, enabling people to perform better on tasks involving working memory.

The hope is that the approach could one day be used to bypass damaged areas of the brain and relay signals in people with traumatic brain injury, stroke or epilepsy.

The brain is in a constant state of chatter, with this activity seen as brainwaves oscillating at different frequencies and different regions keeping a steady ‘beat’.

We are very excited about the potential of brain stimulation to treat patients

– Professor David Sharp

Neurologist in Imperial’s Department of Medicine

In a small study, published today in the journal eLife, the Imperial team found that applying a weak electrical current through the scalp helped to align different parts of the brain, synchronising their brain waves and enabling them to keep the same beat.

“What we observed is that people performed better when the two waves had the same rhythm and at the same time,” said Dr Ines Ribeiro Violante, a neuroscientist in the Department of Medicine at Imperial, who led the research.

In the trial, carried out in collaboration with University College London, the team used a technique called transcranial alternating current stimulation (TACS) to manipulate the brain’s regular rhythm.

They found that buzzing the brain with electricity could give a performance boost to the same memory processes used when people try to remember names at a party, telephone numbers, or even a short grocery list.

Keeping the beat

Dr Violante and team used TACS to target two brain regions – the middle frontal gyrus and the inferior parietal lobule – which are known to be involved in working memory.

Ten volunteers were asked to carry out a set of memory tasks of increasing difficulty while receiving theta frequency stimulation to the two brain regions at slightly different times (unsynchronised), at the same time (synchronous), or only a quick burst (sham) to give the impression of receiving full treatment.

In the working memory experiments, participants looked at a screen on which numbers flashed up and had to remember if a number was the same as the previous, or in the case of the harder trial, if it the current number matched that of two-numbers previous.

The hope is that it could eventually be used for these patients, or even those who have suffered a stroke or who have epilepsy.

– Ines Rebeiro Violante

Lead author

Results showed that when the brain regions were stimulated in sync, reaction times on the memory tasks improved, especially on the harder of the tasks requiring volunteers to hold two strings of numbers in their minds.

“The classic behaviour is to do slower on the harder cognitive task, but people performed faster with synchronised stimulation and as fast as on the simpler task,” said Dr Violante.

Previous studies have shown that brain stimulation with electromagnetic waves or electrical current can have an effect on brain activity, the field has remained controversial due to a lack of reproducibility.

But using functional MRI to image the brain enabled the team to show changes in activity occurring during stimulation, with the electrical current potentially modulating the flow of information.

“We can use TACS to manipulate the activity of key brain networks and we can see what’s happening with fMRI,” explained Dr Violante.

“The results show that when the stimulation was in sync, there was an increase in activity in those regions involved in the task. When it was out of sync the opposite effect was seen.”

However, one of the major hurdles for making such a treatment widely available is the individual nature of people’s brains. Not only do the electrodes have to get the right frequency, but target it to the right part of the brain and get the beat in time.

Dr Violante added: “We use a very cheap technique, and that’s one of the advantages we hope it will bring if it’s translatable to the clinic.

“The next step is to see if the brain stimulation works in patients with brain injury, in combination with brain imaging, where patients have lesions which impair long range communication in their brains.

“The hope is that it could eventually be used for these patients, or even those who have suffered a stroke or who have epilepsy.”

Professor David Sharp, a neurologist in Imperial’s Department of Medicine and senior author on the paper, added: “We are very excited about the potential of brain stimulation to treat patients. I work with patients who often have major problems with working memory after their head injuries, so it would be great to have a way to enhance our current treatments, which may not always work for them.

“Our next step is to try the approach out in our patients and we will see whether combining it with cognitive training can restore lost skills.”

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New clot-busting treatment targets number one killer

Nanotechnology developed to help treat heart attack and stroke.

Nanotechnology developed to help treat heart attack and stroke.

Australian researchers funded by the National Heart Foundation are a step closer to a safer and more effective way to treat heart attack and stroke via nanotechnology.

The research jointly lead by Professor Christoph Hagemeyer, Head of the Vascular Biotechnology Laboratory at Baker IDI Heart and Diabetes Institute and Professor Frank Caruso, an ARC Australian Laureate Fellow in the Department of Chemical and Biomolecular Engineering at the University of Melbourne, was published today in the leading journal Advanced Materials.

Professor Hagemeyer said this latest step offers a revolutionary difference between the current treatments for blood clots and what might be possible in the future.

This life saving treatment could be administered by paramedics in emergency situations without the need for specialised equipment as is currently the case.

“We’ve created a nanocapsule that contains a clot-busting drug. The drug-loaded nanocapsule is coated with an antibody that specifically targets activated platelets, the cells that form blood clots,” Professor Hagemeyer said.

“Once located at the site of the blood clot, thrombin (a molecule at the centre of the clotting process) breaks open the outer layer of the nanocapsule, releasing the clot-busting drug. We are effectively hijacking the blood clotting system to initiate the removal of the blockage in the blood vessel,” he said.

Professor Frank Caruso from the Melbourne School of Engineering said the targeted drug with its novel delivery method can potentially offer a safer alternative with fewer side effects for people suffering a heart attack or stroke.

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Stem cells show promise for stroke in pilot study

MRI scans showing brain damage in the stroke patients before treatment. Source: Stem Cells Translational Medicine.

MRI scans showing brain damage in the stroke patients before treatment. Source: Stem Cells Translational Medicine.

A stroke therapy using stem cells extracted from patients’ bone marrow has shown promising results in the first trial of its kind in humans.

Five patients received the treatment in a pilot study conducted by doctors at Imperial College Healthcare NHS Trust and scientists at Imperial College London.

The therapy was found to be safe, and all the patients showed improvements in clinical measures of disability.

The findings are published in the journal Stem Cells Translational Medicine. It is the first UK human trial of a stem cell treatment for acute stroke to be published.

The therapy uses a type of cell called CD34+ cells, a set of stem cells in the bone marrow that give rise to blood cells and blood vessel lining cells. Previous research has shown that treatment using these cells can significantly improve recovery from stroke in animals. Rather than developing into brain cells themselves, the cells are thought to release chemicals that trigger the growth of new brain tissue and new blood vessels in the area damaged by stroke.

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‘Robust’ Treatment for Stroke Uses Genetic Material From Bone Marrow

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“In this study we pioneered a totally new treatment for stroke, and possibly for all neurological disease”

In the latest in a series of experiments testing the use of stem cells to treat neurological disease, researchers at Henry Ford Hospital have shown for the first time that microscopic material in the cells offers a “robust” treatment for crippling stroke.

“In this study we pioneered a totally new treatment for stroke, and possibly for all neurological disease,” says Michael Chopp, Ph.D., scientific director of the Henry Ford Neuroscience Institute.

The new study is published online in the current issue of Journal of Cerebral Blood Flow and Metabolism.

It focused on exosomes, blister-like microscopic “bubbles” that once were thought to carry and get rid of “old” proteins that were no longer needed by the body. After they were recently found to also carry RNA, whole new fields of study were suggested – including the pioneering work at Henry Ford.

The research team found that after inducing stroke in lab rats, injecting exosomes containing this genetic material into their blood prompted remodeling of the affected brain, including increased production of new brain cells, blood vessels and neural rewiring. Together, these effects significantly improved neurological function that had been impaired by stroke.

Using bone marrow from the adult rats, the researchers extracted stem cells – specifically mesenchymal cells, or MSCs – that were then employed to generate exosomes.

The researchers induced stroke by occluding an artery in the brain of each rat to block blood flow for two hours. Twenty-four hours later, they injected the exosomes into a vein in each rat’s tail.

The rats’ physical agility and neurological responses were tested before stroke and after treatment with the exosomes, and the results were compared.

“All rats showed severe functional loss one day after treatment, but gradual and eventually significant improvement during the four-week period that followed,” Dr. Chopp says. “This discovery provides a novel treatment for stroke, and possibly other neurological diseases.”

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SLAC invention measures stroke damage in the brain

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Research that could lead to new medical imaging methods and better treatments for stroke and other brain conditions

A technique Stanford Linear Accelerator Center (SLAC) scientists invented for scanning ancient manuscripts is now being used to probe the human brain, in research that could lead to new medical imaging methods and better treatments for stroke and other brain conditions.

The studies, taking place at SLAC’s Stanford Synchrotron Radiation Lightsource, are led by cell biologist Helen Nichol, of the University of Saskatchewan, with $2.5 million in funding from the Canadian government and the Heart and Stroke Foundation of Canada.

Her team, which includes a Stanford neurosurgeon and stem cell expert, other medical doctors and experts in stroke research and medical imaging, reflects the broad ambitions of this research: to give doctors a better understanding of what they’re seeing in MRI scans of stroke patients; to improve diagnosis and guide treatments; and maybe even to develop new ways to peer inside the living brain. What all these goals have in common is that they depend on the ability to track movements and deposits of tiny traces of metal in human tissue. That’s a job the SSRL technique, known as rapid-scanning XRF, is exquisitely suited to do.

At a synchrotron equipped with this technology, “you can see a large sample of brain, and you have the high resolution the technique offers to actually zoom in on your single cells,” said Dr. Raphael Guzman, a pediatric neurosurgeon and stem cell expert at Stanford University Medical Center who is leading part of the study.

Regular XRF, or X-ray fluorescence imaging, uses the SSRL’s powerful X-ray beam to knock electrons out of the inner shells of atoms in a sample. As more electrons fall in to fill the gaps, they give off light—fluoresce—and the color of that light reveals which chemical elements are present.

In the mid-2000s, SLAC scientists had a chance to use this technique to examine a priceless manuscript—the Archimedes palimpsest, a 10th century parchment containing copies of works by the ancient Greek mathematician that had been erased by monks and recycled as a prayer book. But they soon realized that to examine something this big in a reasonable amount of time, they would have to make the scanning go much faster.

Led by physicist Uwe Bergmann, they developed a way to move the beam continually over the sample, rather than imaging one spot at a time. This allowed them to proceed 300 times faster—a scan that used to take 12 days could now be done in an hour—and opened up the possibility of examining much bigger samples, from art objects and cultural artifacts to fossils of early birds. In 2006, Bergmann and an international team of researchers used rapid-scanning XRF to reveal the words of Archimedes, including passages that had been lost for centuries, beneath the prayer writings on the old parchment.

When she read about this research, Nichol said, “It just grabbed me. I thought, if he could map something as big as a sheet of paper, we could map a brain.”

She and her colleagues began using rapid-scanning XRF at the SSRL to look at metals in the preserved brains of people who had died with Alzheimer’s disease, Parkinson’s disease or multiple sclerosis. The healthy brain needs metals like iron, zinc, manganese and copper to work properly, and some studies had indicated that in people with neurodegenerative diseases, the normal distribution of these metals was out of whack.  But did these changes cause the disease, or were they a result of it? And were they consistent enough to offer a tool for diagnosis?

To the team’s disappointment, scans of brain slices from eight people with Parkinson’s disease found no clear pattern—nothing that could help doctors diagnose their brain conditions or understand how they came about. “What we found is that the changes you see in Parkinson’s and Alzheimer’s are sort of variations on normal,” Nichol said.

She decided that beam time on the SSRL was better spent studying a disorder that caused clear, obvious damage in the brain. Stroke fit the bill.

When a stroke blocks the flow of blood to the brain, it produces striking lesions, almost like bruises, caused by bleeding and tissue death. Blood contains iron, which is part of the hemoglobin that carries oxygen in red blood cells. When bleeding occurs, the iron leaks out in a form that can damage surrounding cells, so the body quickly tucks the iron away in various chemical compounds for safe storage.

Standard MRI scans can image and identify those iron compounds and show doctors where bleeding has taken place. But they may not catch the very smallest bleeds, Nichol said, or identify other elements that may be disrupted during a stroke.

That’s where RS-XRF comes in. As the first practical tool for imaging a number of different metals in all of their chemical forms at the same time—and over a large section of the brain—it “opens up a lot of doors to things you can’t see with medical imaging,” Nichol said. It also can tell one form of iron from another; the spectrum of iron in hemoglobin will look different than free-floating iron or the iron compounds produced by bleeding, for instance.

The idea behind the study is that iron in its varied forms can be used as a marker to reveal changes in molecules and cells that follow a stroke, evaluate stroke damage and follow the migration of stem cells that are injected into patients in experimental stroke treatments. The scientists will also look at sulfur compounds that are thought to play a role in protecting the brain from damage, and evaluate the effects of the few stroke treatments available, such as chilling the brain, on the distribution of iron and sulfur.

Members of the team come to the SSRL about three weeks per year to scan brain tissue from rats, including some that have been bred to make them unusually susceptible to stroke, as well as human brain tissue from the National Institutes of Health brain bank. Additional experiments are being done at the Canadian Light Source at the University of Saskatchewan.

While they are not putting live patients in a synchrotron, the scientists hope their findings will someday result in the ability to scan live patients with methods that are much more sensitive to damage from tiny strokes that now go unnoticed.

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