Neuroscience

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Flipping on the Lights to Halt Seizures

Targeted light transmission to genetically altered brain cells stops seizures cold.

Strobe lights can trigger epileptic seizures. Now imagine a light that stops a seizure a split second after it starts. 

By applying pulses of light to genetically altered nerve cells deep in rat brains, researchers at Stanford and Pierre and Marie Curie University in France have done just that. Their results, which showed for the first time how a part of the brain called the thalamus is involved with epileptic seizures, were published in Nature Neuroscience.

The study could point toward new targets for epilepsy treatment, says Ed Boyden, associate professor and leader of the Synthetic Biology Group at MIT. Boyden was not involved in the work. Some ideas “might emerge immediately from knowing new targets to insert deep brain stimulation electrodes,” a type of device already used to help people with epilepsy, Boyden says.

The latest research looked at a kind of seizure that sometimes follows damage to the cerebral cortex, the outer part of the brain, from strokes or head injuries. Previous reports had hinted that the cortex might also communicate during a seizure with the thalamus, the brain’s message relay center.

In the current study, experiments with rats confirmed that the thalamus propagates seizure activity originating in the cortex. To see if the thalamus could be a target for treating seizures, Jeanne Paz, the paper’s lead author, and her colleagues turned to optogenetics, a technology that lets researchers use light to turn brain cells on and off.

For the “genetics” part, they used a virus to insert the DNA code for a light-sensitive protein into thalamus cells of rats. When exposed to light, the protein interferes with these cells’ ability to communicate.

The researchers then developed a light source that would turn on only when a rat had a seizure. To detect seizures, they implanted electrodes into the rats’ brains. When these electrodes registered a seizure starting, light from a laser was aimed directly at the genetically altered thalamus cells. The result, the researchers found, was that flipping on the light immediately stopped the seizure activity, proving that the thalamus is needed to keep seizures going.

“We’re excited that just a brief light exposure was enough to stop the seizure,” says John Huguenard, Stanford professor of neurology and neurological sciences and an author of the study.

However, Huguenard says, an optogenetics-based brain implant to control seizures is a long way off because of the unknown risks of altering a person’s DNA with a virus. “I would want to be cautious,” he says.

(Source: technologyreview.com)

Filed under brain brain cells seizures optogenetics light neuroscience science

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New epilepsy gene discovered
In a national research partnership, Dr Sarah Heron from the University of South Australia’s Sansom Research Institute, epilepsy research group, has been working to map the genes responsible for a rare form of epilepsy - autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE).
Dr Heron and her team’s latest research to identify a new gene for this form of epilepsy has been published in Nature Genetics this month. 
She says while ADNFLE affects a relatively rare group of people, the symptoms and impact of the condition can be devastating.
“ADNFLE usually develops in childhood and characterised by clusters of seizures during sleep,” Dr Heron says.
“It can have an association with cognitive deficits and or psychiatric comorbidity.
“Our research has identified that mutations in the sodium-gated potassium channel gene KCNT1 cause severe autosomal dominant nocturnal frontal lobe epilepsy and associated intellectual and or psychiatric disability.”
Dr Heron says the identification of the gene has important implications for genetic counselling and also for understanding more about the full spectrum of epilepsy disorders.

New epilepsy gene discovered

In a national research partnership, Dr Sarah Heron from the University of South Australia’s Sansom Research Institute, epilepsy research group, has been working to map the genes responsible for a rare form of epilepsy - autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE).

Dr Heron and her team’s latest research to identify a new gene for this form of epilepsy has been published in Nature Genetics this month. 

She says while ADNFLE affects a relatively rare group of people, the symptoms and impact of the condition can be devastating.

“ADNFLE usually develops in childhood and characterised by clusters of seizures during sleep,” Dr Heron says.

“It can have an association with cognitive deficits and or psychiatric comorbidity.

“Our research has identified that mutations in the sodium-gated potassium channel gene KCNT1 cause severe autosomal dominant nocturnal frontal lobe epilepsy and associated intellectual and or psychiatric disability.”

Dr Heron says the identification of the gene has important implications for genetic counselling and also for understanding more about the full spectrum of epilepsy disorders.

Filed under genes epilepsy seizures genetics neuroscience science

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A Future Without Seizures
Five-year-old Nathan Kalina of Naperville will enter kindergarten this fall after spending the summer in day camp: playing games, enjoying field trips, and romping in the pool. He loves playing with action figures and acting out scenes from his favorite movies.
The scene two years ago was very different. After getting a few reports from daycare about unexplained falls, Nathan’s parents started to notice him having minor seizures. His mother, Megan, wasn’t too concerned at first; both she and her father had had childhood seizures and recovered from them without incident. Then came Nathan’s first tonic-clonic seizure (formerly known as a “grand mal” seizure), a major event involving his whole brain and body. A trip to a local emergency room for basic tests led to an electroencephalogram a few days later. All the while Nathan was having more seizures, large and small.
"We went from zero to crazy in a matter of days," Megan said.
Medication helped some. Nathan’s father David, a teacher in the Naperville schools, devoted his summer to adjusting Nathan’s regimen. But in the fall, the seizures ramped up again. One specialist suggested a high-fat ketogenic diet, which has been shown to help some children with epilepsy — but it didn’t help Nathan. “Feeding a 4-year-old picky eater on meat, cheese and cream was hard on us and started making him sick,” Megan said.

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A Future Without Seizures

Five-year-old Nathan Kalina of Naperville will enter kindergarten this fall after spending the summer in day camp: playing games, enjoying field trips, and romping in the pool. He loves playing with action figures and acting out scenes from his favorite movies.

The scene two years ago was very different. After getting a few reports from daycare about unexplained falls, Nathan’s parents started to notice him having minor seizures. His mother, Megan, wasn’t too concerned at first; both she and her father had had childhood seizures and recovered from them without incident. Then came Nathan’s first tonic-clonic seizure (formerly known as a “grand mal” seizure), a major event involving his whole brain and body. A trip to a local emergency room for basic tests led to an electroencephalogram a few days later. All the while Nathan was having more seizures, large and small.

"We went from zero to crazy in a matter of days," Megan said.

Medication helped some. Nathan’s father David, a teacher in the Naperville schools, devoted his summer to adjusting Nathan’s regimen. But in the fall, the seizures ramped up again. One specialist suggested a high-fat ketogenic diet, which has been shown to help some children with epilepsy — but it didn’t help Nathan. “Feeding a 4-year-old picky eater on meat, cheese and cream was hard on us and started making him sick,” Megan said.

Read more

Filed under brain epilepsy seizures brain mapping neuroscience psychology science

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Scientists have discovered the first direct evidence that a biological mechanism long suspected in epilepsy is capable of triggering the brain seizures – opening the door for studies to seek improved treatments or even preventative therapies.
Researchers at Cincinnati Children’s Hospital Medical Center report Sept. 19 in Neuron that molecular disruptions in small neurons called granule cells – located in the dentate gyrus region of the brain – caused brain seizures in mice similar to those seen in human temporal lobe epilepsy. The dentate gyrus is in the hippocampus of the temporal lobe, and temporal lobe epilepsy is one of the most common forms of the disorder.
“Epilepsy is one of those rare disorders where we have no real preventative therapies, and current treatments after diagnosis can have significant side effects,” said Steven Danzer, PhD, principal investigator on the study and a neuroscientist in the Department of Anesthesia at Cincinnati Children’s. “Establishing which cells and mechanisms are responsible for the seizures allows us to begin working on ways to control or eliminate the problem therapeutically, and in a more precise manner.”

Scientists have discovered the first direct evidence that a biological mechanism long suspected in epilepsy is capable of triggering the brain seizures – opening the door for studies to seek improved treatments or even preventative therapies.

Researchers at Cincinnati Children’s Hospital Medical Center report Sept. 19 in Neuron that molecular disruptions in small neurons called granule cells – located in the dentate gyrus region of the brain – caused brain seizures in mice similar to those seen in human temporal lobe epilepsy. The dentate gyrus is in the hippocampus of the temporal lobe, and temporal lobe epilepsy is one of the most common forms of the disorder.

“Epilepsy is one of those rare disorders where we have no real preventative therapies, and current treatments after diagnosis can have significant side effects,” said Steven Danzer, PhD, principal investigator on the study and a neuroscientist in the Department of Anesthesia at Cincinnati Children’s. “Establishing which cells and mechanisms are responsible for the seizures allows us to begin working on ways to control or eliminate the problem therapeutically, and in a more precise manner.”

Filed under DGCs brain epilepsy neuroscience psychology seizures science

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Yale researchers studying epileptic seizures have shed new light on the neurological origins of consciousness.
When epileptics lose consciousness during a variety of types of seizures, the signals converge on the same brain structures, but through different pathways, says Dr. Hal Blumenfeld, professor of neurology, neurobiology, and neurosurgery.
“Understanding of these mechanisms could lead to improved treatment strategies to prevent impairment of consciousness and improve the quality of life of people with epilepsy,” he said.
Blumenfeld’s research is described in the current issue of the journal Lancet Neurology.
(Image: The fMRI images are different viewpoints of the brain of a child experiencing an epileptic seizure. Areas in yellow and orange represent increased brain activity compared to its normal state, while areas in blue show decreased activity. These are the areas of the brain needed for normal consciousness.)

Yale researchers studying epileptic seizures have shed new light on the neurological origins of consciousness.

When epileptics lose consciousness during a variety of types of seizures, the signals converge on the same brain structures, but through different pathways, says Dr. Hal Blumenfeld, professor of neurology, neurobiology, and neurosurgery.

“Understanding of these mechanisms could lead to improved treatment strategies to prevent impairment of consciousness and improve the quality of life of people with epilepsy,” he said.

Blumenfeld’s research is described in the current issue of the journal Lancet Neurology.

(Image: The fMRI images are different viewpoints of the brain of a child experiencing an epileptic seizure. Areas in yellow and orange represent increased brain activity compared to its normal state, while areas in blue show decreased activity. These are the areas of the brain needed for normal consciousness.)

Filed under consciousness epilepsy seizures science brain psychology neuroscience

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Electrical Brain Stimulation Curbs Epileptic Seizures in Rats

THURSDAY, Aug. 9 (HealthDay News) — Researchers report that they have created a device able to short-circuit epileptic seizures in rats.

Similar in design to an implantable defibrillator, the device is placed in the brain and reacts only when a seizure starts to occur, essentially aborting the seizure’s electrical activity.

The self-adjusting device electrically stimulates the brain at the beginning of a short but frequent type of seizure in rats, and then automatically shuts itself off. The research was published in the Aug. 10 issue of the journal Science.

"It works like a ping-pong game," explained study author Dr. Gyorgy Buzsaki, a professor of neural science at New York University. "Every time a ball is coming your way, you apply an interfering pattern to whack it away."

Epilepsy is a brain disorder in which a person has repeated seizures over time. It affects nearly 3 million Americans, according to the Epilepsy Foundation, making it the third most common neurological disorder in the United States, after Alzheimer’s and stroke.

People with epilepsy can suffer from two different kinds of seizures: petit mal seizures, which last for just a few seconds but can occur frequently, and grand mal seizures, which are rare but involve violent muscle contractions and a loss of consciousness.

Seizures are episodes of disturbed brain activity that cause changes in attention or behavior. Brain cells keep firing instead of acting in an organized way. The malfunctioning electrical system of the brain causes surges of energy that can cause unconsciousness and muscle contractions.

The researchers tested the new device against petit mal seizures in rats because this type of seizure occurs hundreds of times a day. The sheer volume of the seizures allowed the scientists to effectively test the system they designed. People with petit mal seizures are typically treated effectively with drugs, so the device would not be used to treat that type of seizure.

In what Buzsaki describes as a simple, closed-loop system, the firing of brain neurons creates a spike in neurological activity that is followed by a wave and detected by the device, which fires back only when necessary. The system, called transcranial electrical stimulation, leaves other aspects of brain function unaffected. “The system doesn’t prevent seizures, it just treats them right away,” said Buzsaki. The stimulation reduced the length of a seizure by about 60 percent.

In humans, two plates about the size of a pocket watch could be placed in the skull in a position designed to target the affected area of the brain. The electrodes would be powered by ultralight electrical circuits implanted in the skull, Buzsaki explained.

The goal is to apply the system that worked in rats to people with complex partial seizures — epileptic seizures that affect both sides of the brain and cause a loss of consciousness, Buzsaki said. Although the device worked in rats, the results may not translate to humans.

This type of seizure also can occur with head injuries, brain infection and stroke. The cause is typically unknown.

In 20 percent to 40 percent of people who have complex partial seizures, drugs are ineffective and there are no remedies, Buzsaki said. “It’s not clear what kind of stimulation to deliver and where exactly in the brain the stimulation should go,” he explained.

Dr. Orrin Devinsky, director of the epilepsy program at New York University, said the research has enormous potential for treating epilepsy and other neurological problems. “What’s unique about this technique is that it’s a sophisticated way to identify the rhythmicity of the seizure itself and interrupt the cycle with precision,” he said. “Existing [deep brain stimulation] devices don’t finesse the timing this way.”

Devinsky, who was not associated with the study, said the research could potentially be applicable to people with tremors, Parkinson’s disease and even those with serious depression and other psychological disorders.

Source: HealthDay

Filed under science neuroscience brain psychology epilepsy stimulation seizures

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Musical brain patterns could help predict epileptic seizures

June 15, 2012

The research led by Newcastle University’s Dr Mark Cunningham and Professor Miles Whittington and supported by the Dr Hadwen Trust for Humane Research, indicates a novel electrical bio-marker in humans.

The brain produces electrical rhythms and using EEG - electrodes on the scalp - researchers were able to monitor the brain patterns in patients with epilepsy. Both in patients and in brain tissue samples the team were able to witness an abnormal brain wave noticeable due to its rapidly increasing frequency over time.

Comparing these to a musical ‘glissando’, an upwards glide from one pitch to another, the team found that this brain rhythm is unique to humans and they believe it could be related to epilepsy.

Dr Cunningham, senior lecturer in Neuronal Dynamics at Newcastle University said: “We were able to examine EEG collected from patients with drug resistant epilepsy who were continually monitored over a two week period. During that time we noticed patterns of electrical activity with rapidly increasing frequency, just like glissandi, emerging in the lead-up to an epileptic seizure.”

"We are in the early days of the work and we want to investigate this in a larger group of patients but it may offer a promising insight into when a seizure is going to start."

Professor Whittington added: “Classical composers such as Gustav Mahler are famous for using notes of rapidly increasing pitch – called glissando - to convey intense expressions of anticipation. Similarly we identified glissando-like patterns of brain electrical activity generated in anticipation of seizures in patients with epilepsy.”

The team recorded electrical activity taken from patients in Newcastle and Glasgow with the help of collaborators Dr Roderick Duncan and Dr Aline Russell and worked in collaboration with the Epilepsy Surgery Group at Newcastle General Hospital part of the Newcastle Hospitals NHS Foundation Trust.

Having received permission from patients to use brain tissue removed during an operation to cure their seizures, the team were able to observe and study in great detail glissando discharges in slices of this human epileptic tissue maintained in the lab.

Publishing in Epilepsia online, the team discovered that glissandi are highly indicative of pathology associated with human epilepsy and, unlike other forms of epileptic activity studied previously, are extremely difficult to reproduce in normal, non-epileptic brain tissue. The team worked with Professor Roger Traub at the IBM Watson Research Centre in New York to provide predictions using highly detailed computational models. By manipulating the chemical conditions surrounding human epileptic brain tissue according to these predictions, they discovered that glissandi did not require any of the conventional chemical connections between nerve cells thought to underlie most brain functions. Instead, glissandi were generated by a combination of large changes in the pH of the tissue, specific electrical properties of certain types of nerve cell and, most importantly, direct electrical connections between these nerve cells.

"This work also suggests that given the lengths one has to go to reproduce this experimentally in rodents that the glissandi may be a unique feature of the human epileptic brain," explains Dr Cunningham.

Dr Kailah Eglington, Chief Executive of the Dr Hadwen Trust, said: “Of all human brain disorders, epilepsy research ranks as one that currently employs substantial numbers of laboratory animals worldwide.

"Dr Cunningham’s work at Newcastle University aims to address the shortcomings of existing animal-based research by removing animals from the equation and addressing the issue directly in humans."

Provided by Newcastle University

Source: medicalxpress.com

Filed under science neuroscience brain psychology seizures

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