Posts Tagged Cortex

[NEWS] Scientists can monitor brain activity to predict epileptic seizures few minutes in advance

 

Elizabeth Delacruz can’t crawl or toddle around like most youngsters nearing their second birthday.

A rare metabolic disorder that decimated her mobility has also led to cortical blindness – her brain is unable to process images received from an otherwise healthy set of brown eyes. And multiple times a day Elizabeth suffers seizures that continually reduce her brain function. She can only offer an occasional smile or make soft bubbly sounds to communicate her mood.

“But a few months ago I heard her say, ‘Mama,’ and I started to cry,” said Carmen Mejia, a subtle quaver in her voice as she recalled the joy of hearing her daughter. “That’s the first time she said something.”

Ms. Mejia realizes it may also be the last, unless doctors can find a way to detect and prevent the epileptic seizures stemming from a terminal disease called pyruvate dehydrogenase deficiency (PDHD) – which occurs when mitochondria don’t provide enough energy for the cells.

A UT Southwestern study gives parents like Ms. Mejia renewed hope for their children: By monitoring the brain activity of a specific cell type responsible for seizures, scientists can predict convulsions at least four minutes in advance in both humans and mice. The research further shows that an edible acid called acetate may effectively prevent seizures if they are detected with enough notice.

Although the prediction strategy cannot yet be used clinically – a mobile technology for measuring brain activity would have to be developed – it signifies a potential breakthrough in a field that had only been able to forecast seizures a few seconds ahead.

“Many of the families I meet with are not just bothered by the seizures. The problem is the unpredictability, the not knowing when and where a seizure might occur,” said Dr. Juan Pascual, a pediatric neurologist with UT Southwestern’s O’Donnell Brain Institute who led the study published in Science Translational Medicine. “We’ve found a new approach that may one day solve this issue and hopefully help other scientists track down the root of seizures for many kinds of epilepsy.”

Debunked theory

The critical difference between the study and previous efforts was debunking the long-held belief among researchers that most cells in epilepsy patients have malfunctioning mitochondria. In fact, Dr. Pascual’s team spent a decade developing a PDHD mouse model that enabled them to first discover the key metabolic defect in the brain and then determine only a single neuron type was responsible for seizures as the result of the metabolic defect. They honed in on these neurons’ electrical activity with an electroencephalogram (EEG) to detect which brainwave readings signaled an upcoming seizure.

“It’s much more difficult to predict seizures if you don’t know the cell type and what its activity looks like on the EEG,” Dr. Pascual said. “Until this finding, we thought it was a global deficiency in the cells and so we didn’t even know to look for a specific type.”

Predicting seizures

The study shows how a PDHD mouse model helped scientists trace the seizures to inhibitory neurons near the cortex that normally keep the brain’s electrical activity in check.

Scientists then tested a method of calculating when seizures would occur in mice and humans by reviewing EEG files and looking for decreased activity in energy-deficient neurons. Their calculations enabled them to forecast 98 percent of the convulsions at least four minutes in advance.

Dr. Pascual is hopeful his lab can refine EEG analyses to extend the warning window by several more minutes. Even then, live, clinical predictions won’t be feasible unless scientists develop technology to automatically interpret the brain activity and calculate when a seizure is imminent.

Still, he said, the discovery that a single cell type can be used to forecast seizures is a paradigm-shifting finding that may apply to all mitochondrial diseases and related epilepsies.

Potential therapy

Dr. Pascual’s ongoing efforts to extend the prediction time may be a crucial step in utilizing the other intriguing finding from the study: the use of acetate to prevent seizures.

The study showed that delivering acetate into the blood stream of PDHD mice gave their neurons enough energy to normalize their activity and decrease seizures for as long as the acetate was in the brain. However, Dr. Pascual said the acetate would probably need more time – perhaps 10 minutes or more – to take effect in humans if taken by mouth.

Acetate, which naturally occurs in some foods, has been used in patients for decades – including newborns needing intravenous nutrition or patients whose metabolism has shut down. But it had not yet been established as an effective treatment for mitochondrial diseases that underlie epilepsy.

Among the reasons, Dr. Pascual said, is that labs have struggled to create an animal model of such diseases to study its effects; his own lab spent about a decade doing so. Another is the widespread acceptance of the ketogenic diet to reduce the frequency of seizures.

But amid a growing concern about potentially unhealthy side effects of ketogenic diets, Dr. Pascual has been researching alternatives that may refuel the brain more safely and improve cognition.

Frequent seizures

Elizabeth, among a handful of patients whose EEG data were used in the new study, has been prescribed a ketogenic diet and some vitamins to control the seizures. Her family has seen little improvement. Elizabeth often has more than a dozen seizures a day and her muscles and cognition continue to decline. She can’t hold her head up and her mother wonders how many more seizures her brain can take.

Elizabeth was only a few months old when she was diagnosed with PDHD, which occurs when cells lack certain enzymes to efficiently convert food into energy. Patients who show such early signs often don’t survive beyond a few years.

Ms. Mejia does what she can to comfort her daughter, with the hope that Dr. Pascual’s work can someday change the prognosis for PDHD. Ms. Mejia sings, talks, and offers stuffed animals and other toys to her daughter. Although her little girl can’t see, the objects offer a degree of mental stimulation, she said.

“It’s so hard to see her go through this,” Ms. Mejia said. “Every time she has a seizure, her brain is getting worse. I still hope one day she can get a treatment that could stop all this and make her life better.”

‘Big questions’

Dr. Pascual is already conducting further research into acetate treatments, with the goal of launching a clinical trial for patients like Elizabeth in the coming years.

His lab is also researching other epilepsy conditions – such as glucose transporter type I (Glut1) deficiency – to determine if inhibitory neurons in other parts of the brain are responsible for seizures. If so, the findings could provide strong evidence for where scientists should look in the brain to detect and prevent misfiring neurons.

“It’s an exciting time, but there is much that needs to happen to make this research helpful to patients,” Dr. Pascual said. “How do we find an automated way of detecting neuron activity when patients are away from the lab? What are the best ways to intervene when we know a seizure is coming? These are big questions the field still needs to answer.”

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[WEB SITE] Brain recovery: Activity, not rest, may speed recovery after brain injury – ScienceDaily

Summary:
When recovering from a brain injury, getting back in the swing of things may be more effective than a prolonged period of rest, according to a new study in mice. These findings offer a compelling example of the brain’s remarkable capacity to adapt in response to trauma. They also point to new, activity-centered treatment strategies that could one day result in faster and more complete recovery times for patients looking to regain mobility after a brain damage or a stroke.
FULL STORY

When recovering from a brain injury, getting back in the swing of things may be more effective than a prolonged period of rest, according to a new Columbia study in mice. These findings offer a compelling example of the brain’s remarkable capacity to adapt in response to trauma. They also point to new, activity-centered treatment strategies that could one day result in faster and more complete recovery times for patients looking to regain mobility after a brain damage or a stroke.

This research was reported today in the journal Nature.

“Lengthy rest periods are supposed to be key to the brain’s healthy recovery, but our study in mice demonstrates that re-engaging the brain immediately after injury can actually be more helpful than resting it — an observation that was completely unexpected,” said Randy Bruno, PhD, the study’s senior author and a principal investigator at Columbia’s Mortimer B. Zuckerman Mind Brain Behavior Institute. “While these findings underscore the brain’s complexity, the nature of which we are only beginning to tease apart, they also provide a new avenue of research into more effective rehabilitation efforts for serious brain injuries.”

Today’s study marks an important step in the research team’s multi-year effort to unravel the workings of the brain’s cerebral cortex. The cerebral cortex is the largest region of the mammalian brain and plays a key role in many functions, from sight and smell to movement and memory. For this study in mice, researchers focused on a part of the animals’ cerebral cortex called the barrel cortex, which is thought to be critical for sensing and analyzing signals during whisking, when a mouse moves its whiskers to strike objects.

“Mice use whiskers to sense their surroundings the way we use our fingers,” said Y. Kate Hong, PhD, a postdoctoral associate in the Bruno lab and the paper’s first author.

The researchers placed mice in a dark box and trained them to search for a nearby object with their whiskers. When the mice detected the object, they pulled a lever with their paw to dispense water as a reward. Conventional wisdom argued that this kind of detection task depends almost entirely on a functioning sensory cortex — in this case, the barrel cortex.

To confirm this was true, the researchers used laser light to temporarily turn off barrel-cortex cells, a popular technique known as optogenetics. As expected, animals had difficulty whisking while the cells were turned off. And when the team then permanently removed their barrel cortex, the animals could not perform the task the next day.

But on day two, the animals’ performance suddenly recovered to original levels. “This came as a huge surprise, since it suggested that tactile sensation, such as whisker-based touch, may not completely rely on the cortex,” said Dr. Hong. “These findings challenge the commonly held, cortex-centric view of how the brain drives touch perception.”

The researchers suspect that other, more primitive brain regions may be involved to a greater degree than previously known — a hypothesis the team is currently investigating.

“Rather than being confined to one particular brain region, sensory information is distributed across many areas,” said Dr. Hong. “This redundancy allows the brain to solve problems in more than one way — and can serve to protect the brain in case of injury.”

But to recover, did the animals simply need a day of rest, or did they need to be re-exposed to the task? To find out, the team performed another round of experiments, with one key difference: They let the mice rest for three days before re-exposing them to the task.

This time, the mice showed incomplete rehabilitation. While they did eventually regain some sensation, they recovered more slowly than the first set of mice. The key to a speedy recovery appeared to lie in re-engaging with the task early — not the passage of time.

As to why all mice perform so poorly during the first 24 hours, regardless of what they do? The reason may lie in the disturbance that the brain has just experienced.

“The cortex connects to almost every other structure in the brain, so manipulating it may temporarily disrupt connected structures — in essence shocking those areas that would normally enable a behavior,” said Dr. Bruno. “Perhaps this sudden and brief loss in sensation is due to that initial disruption to the animals’ abilities — rather than being due to the loss of any information stored in the barrel cortex itself.”

The manipulations undertaken by the Columbia team are not unlike what happens in the brain of a person having a stroke. Dr. Bruno and his team caution that their research on rodents cannot be directly applied to human beings. But they hope their findings will be further explored by neurologists looking to improve recovery times for their patients.

“We tend to immobilize people when they’ve suffered a stroke; the recovery of seemingly simple tasks — walking, grasping — can be a long road,” said Dr. Bruno. “Our findings suggest that maybe, in some cases, patients could be reintroduced to these activities much earlier in order to speed recovery.”

Story Source:

Materials provided by The Zuckerman Institute at Columbia UniversityNote: Content may be edited for style and length.


Journal Reference:

  1. Y. Kate Hong, Clay O. Lacefield, Chris C. Rodgers, Randy M. Bruno. Sensation, movement and learning in the absence of barrel cortexNature, 2018; DOI: 10.1038/s41586-018-0527-y

The Zuckerman Institute at Columbia University. “Brain recovery: Activity, not rest, may speed recovery after brain injury.” ScienceDaily. ScienceDaily, 17 September 2018. <www.sciencedaily.com/releases/2018/09/180917111622.htm>.

 

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[WEB PAGE] Study offers possibility of squelching a focal epilepsy seizure before symptoms appear

Patients with focal epilepsy that does not respond to medications badly need alternative treatments.

In a first-in-humans pilot study, researchers at the University of Alabama at Birmingham have identified a sentinel area of the brain that may give an early warning before clinical seizure manifestations appear. They have also validated an algorithm that can automatically detect that early warning.

These two findings offer the possibility of squelching a focal epilepsy seizure — before the patient feels any symptoms — through neurostimulation of the sentinel area of the brain. This is somewhat akin to the way an implantable defibrillator in the heart can staunch heart arrhythmias before they injure the heart.

In the pilot study, three epilepsy patients undergoing brain surgery to map the source of their focal epilepsy seizures also gave consent to add an investigational aspect to their planned surgeries.

As neurosurgeons inserted long, thin, needle-like electrodes into the brain to map the location of the electrical storm that initiates an epileptic seizure, they also carefully positioned the electrodes to add one more task — simultaneously record the electrical activity at the anterior nucleus of the thalamus.

The thalamus is a structure sitting deep in the brain that is well connected with other parts of the brain. The thalamus controls sleep and wakefulness, so it often is called the “pacemaker” of the brain. Importantly, preclinical studies have shown that focal sources of seizures in the cortex can recruit other parts of the brain to help generate a seizure. One of these recruited areas is the anterior thalamic nucleus.

The UAB team led by Sandipan Pati, M.D., assistant professor of neurology, found that nearly all of the epileptic seizures detected in the three patients — which began in focal areas of the cortex outside of the thalamus — also recruited seizure-like electrical activity in the anterior thalamic nucleus after a very short time lag. Importantly, both of these initial electrical activities appeared before any clinical manifestations of the seizures.

The UAB researchers also used electroencelphalography, or EEG, brain recordings from the patients to develop and validate an algorithm that was able to automatically detect initiation of that seizure-like electrical activity in the anterior thalamic nucleus.

“This exciting finding opens up an avenue to develop brain stimulation therapy that can alter activities in the cortex by stimulating the thalamus in response to a seizure,” Pati said. “Neurostimulation of the thalamus, instead of the cortex, would avoid interference with cognition, in particular, memory.”

“In epilepsy, different aspects of memory go down,” Pati explained. “Particularly long-term memory, like remembering names, or remembering events. The common cause is that epilepsy affects the hippocampus, the structure that is the brain’s memory box.”

Pati said these first three patients were a feasibility study, and none of the patients had complications from their surgeries. The UAB team is now extending the study to another dozen patients to confirm the findings.

“Hopefully, after the bigger group is done, we can consider stimulating the thalamus,” Pati said. That next step would have the goals of improved control of seizures and improved cognition, vigilance and memory for patients.

For epilepsy patients where medications have failed, the surgery to map the source of focal seizures is a prelude to two current treatment options — epilepsy surgery to remove part of the brain or continuous, deep-brain stimulation. If the UAB research is successful, deep brain stimulation would be given automatically, only as the seizure initiates, and it would be targeted at the thalamus, where the stimulation might interfere less with memory.

 

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[WEB SITE] Largest-ever study to examine anatomical alterations in the brains of epilepsy patients

Largest-ever study to examine anatomical alterations in the brains of epilepsy patients 

An international research consortium used neuroimaging techniques to analyze the brains of more than 3,800 volunteers in different countries. The largest study of its kind ever conducted set out to investigate anatomical similarities and differences in the brains of individuals with different types of epilepsy and to seek markers that could help with prognosis and treatment.

Epilepsy’s seizure frequency and severity, as well as the patient’s response to drug therapy, vary with the part of the brain affected and other poorly understood factors. Data from the scientific literature suggests that roughly one-third of patients do not respond well to anti-epileptic drugs. Research has shown that these individuals are more likely to develop cognitive and behavioral impairments over the years.

The new study was conducted by a specific working group within an international consortium called ENIGMA, short for Enhancing NeuroImaging Genetics through Meta-Analysis, established to investigate several neurological and psychiatric diseases. Twenty-four cross-sectional samples from 14 countries were included in the epilepsy study.

Altogether, the study included data for 2,149 people with epilepsy and 1,727 healthy control subjects (with no neurological or psychiatric disorders). The Brazilian Research Institute for Neuroscience and Neurotechnology (BRAINN), which participated in the multicenter study, was the center with the largest sample, comprising 291 patients and 398 controls. Hosted in Brazil, at the State University of Campinas (UNICAMP), BRAINN is a Research, Innovation and Dissemination Center (RIDC http://cepid.fapesp.br/en/home/) supported by the Sao Paulo Research Foundation – FAPESP.

“Each center was responsible for collecting and analyzing data on its own patients. All the material was then sent to the University of Southern California’s Imaging Genetics Center in the US, which consolidated the results and performed a meta-analysis,” said Fernando Cendes, a professor at UNICAMP and coordinator of BRAINN.

A differential study

All volunteers were subjected to MRI scans. According to Cendes, a specific protocol was used to acquire three-dimensional images. “This permitted image post-processing with the aid of computer software, which segmented the images into thousands of anatomical points for individual assessment and comparison,” he said.

According to the researcher, advances in neuroimaging techniques have enabled the detection of structural alterations in the brains of people with epilepsy that hadn’t been noticed previously.

Cendes also highlighted that this is the first epilepsy study built on a really large number of patients, which allowed researchers to obtain more robust data. “There were many discrepancies in earlier studies, which comprised a few dozen or hundred volunteers.”

The patients included in the study were divided into four subgroups: mesial temporal lobe epilepsy (MTLE) with left hippocampal sclerosis, MTLE with right hippocampal sclerosis, idiopathic (genetic) generalized epilepsy, and a fourth group comprising various less common subtypes of the disease.

The analysis covered both patients who had had epilepsy for years and patients who had been diagnosed recently. According to Cendes, the analysis – whose results were published in the international journal Brain – aimed at the identification of atrophied brain regions in which the cortical thickness was smaller than in the control group.

First analysis

The researchers first analyzed data from the four patient subgroups as a whole and compared them with the controls to determine whether there were anatomical alterations common to all forms of epilepsy. “We found that all four subgroups displayed atrophy in areas of the sensitive-motor cortex and also in some parts of the frontal lobe,” Cendes said.

“Ordinary MRI scans don’t show anatomical alterations in cases of genetic generalized epilepsy,” Cendes said. “One of the goals of this study was to confirm whether areas of atrophy also occur in these patients. We found that they do.”

This finding, he added, shows that in the case of MTLE, there are alterations in regions other than those in which seizures are produced (the hippocampus, parahippocampus, and amygdala). Brain impairment is, therefore, more extensive than previously thought.

Cendes also noted that a larger proportion of the brain was compromised in patients who had had the disease for longer. “This reinforces the hypothesis that more brain regions atrophy and more cognitive impairment occurs as the disease progresses.”

The next step was a separate analysis of each patient subgroup in search of alterations that characterize each form of the disease. The findings confirmed, for example, that MTLE with left hippocampal sclerosis is associated with alterations in different neuronal circuits from those associated with MTLE with right hippocampal sclerosis.

“Temporal lobe epilepsy occurs in a specific brain region and is therefore termed a focal form of the disease. It’s also the most common treatment-refractory subtype of epilepsy in adults,” Cendes said. “We know it has different and more severe effects when it involves the left hemisphere than the right. They’re different diseases.”

“These two forms of the disease are not mere mirror-images of each other,” he said. “When the left hemisphere is involved, the seizures are more intense and diffuse. It used to be thought that this happened because the left hemisphere is dominant for language, but this doesn’t appear to be the only reason. Somehow, it’s more vulnerable than the right hemisphere.”

In the GGE group, the researchers observed atrophy in the thalamus, a central deep-lying brain region above the hypothalamus, and in the motor cortex. “These are subtle alterations but were observed in patients with epilepsy and not in the controls,” Cendes said.

Genetic generalized epilepsies (GGEs) may involve all brain regions but can usually be controlled by drugs and are less damaging to patients.

Future developments

From the vantage point of the coordinator for the FAPESP-funded center, the findings published in the article will benefit research in the area and will also have future implications for the diagnosis of the disease. In parallel with their anatomical analysis, the group is also evaluating genetic alterations that may explain certain hereditary patterns in brain atrophy. The results of this genetic analysis will be published soon.

“If we know there are more or less specific signatures of the different epileptic subtypes, instead of looking for alterations everywhere in the brain, we can focus on suspect regions, reducing cost, saving time and bolstering the statistical power of the analysis. Next, we’ll be able to correlate these alterations with cognitive and behavioral dysfunction,” Cendes said.

 

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[REVIEW] Biomechanics and neural control of movement, 20 years later: what have we learned and what has changed? – Full Text

Abstract

We summarize content from the opening thematic session of the 20th anniversary meeting for Biomechanics and Neural Control of Movement (BANCOM). Scientific discoveries from the past 20 years of research are covered, highlighting the impacts of rapid technological, computational, and financial growth on motor control research. We discuss spinal-level communication mechanisms, relationships between muscle structure and function, and direct cortical movement representations that can be decoded in the control of neuroprostheses. In addition to summarizing the rich scientific ideas shared during the session, we reflect on research infrastructure and capacity that contributed to progress in the field, and outline unresolved issues and remaining open questions.

Background

At the 20th anniversary meeting for Biomechanics and Neural Control of Movement (BANCOM), the opening thematic session was chaired by Dr. Fay Horak (Oregon Health & Science University). Presentations and discussions covered insights from 20 years of research in the field of motor control, delivered by Drs. Zev Rymer (Rehabilitation Institute of Chicago), Andy Biewener (Harvard University), Andy Schwartz (University of Pittsburgh), and Daofen Chen (National Institute of Neurological Disorders and Stroke). Presentation themes included the impact of technological advancements on motor control research, unresolved issues in muscle biology and neurophysiology, and changes in the scientific funding landscape. This brief review summarizes content presented by each speaker, along with discussions from the audience.

Considerable changes have occurred in the fields of biomechanics and motor control over the past 20 years, changes made possible by rapid technological advances in computing power and memory along with reduced physical size of biotechnology hardware. Because of these changes, research approaches have been reshaped and new questions have emerged. Previously, motor control research was constrained to laboratory-based assessments of individual neurons, muscles or joints, captured from low sample sizes. In the past, reliance on large, expensive, external recording devices, such as optical motion capture systems, understandably limited the feasibility of large-scale, multivariate research. Today, whole-body kinematic recordings using body-worn inertial measurement units, wireless electromyography (EMG), electroencephalography (EEG), and functional near infrared spectroscopy (fNIRS) systems, and electrode arrays for neural network recordings are increasingly commonplace. Alongside these technical leaps, sociocultural bounds have expanded research inclusion, as evidenced in the representation of speakers at the 2016 BANCOM meeting. In contrast to the 1996 meeting, which included three invited female speakers, 13 women were included as speakers in 2016. Such advancements will continue to shape our scientific landscape, driving innovation through new technologies and perspectives.[…]

Continue —>  Biomechanics and neural control of movement, 20 years later: what have we learned and what has changed? | Journal of NeuroEngineering and Rehabilitation | Full Text

 

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[WEB SITE] Study investigates plasticity of motor representations in patients with brain tumors

Winner of the Brainlab Community Neurosurgery Award, Sandro Krieg, MD, presented his research, Plasticity of Motor Representations in Patients with Brain Lesions: a Navigated TMS Study, during the 2017 American Association of Neurological Surgeons (AANS) Annual Scientific Meeting.

This study investigated the spatial distributions of motor representations in terms of tumor-induced brain plasticity by analyzing navigated transcranial magnetic stimulation (nTMS) motor maps derived from 100 patients with motor eloquently located brain tumors in or adjacent to the precentral gyrus (PrG).

The research evoked 8,774 motor potentials (MEPs) that were elicited in six muscles of the upper and lower extremity by stimulating four gyri in patients with five possible tumor locations. Regarding the MEP frequency of each muscle-gyrus subdivision per patient, the expected frequency was 3.53 (8,774 divided by 100 patients, further divided by six muscles and four gyri). Accordingly, the patient ratio for each subdivision was calculated by defining the per-patient minimum data points as three.

The tumor-location specific patient ratios were higher for frontal tumors in both gyri than for other tumor locations. This suggests that the finger representation reorganization in these frontal gyri, which corresponds to location of dorsal premotor areas, might be due to within-premotor reorganization rather than relocation of motor function from PrG into premotor areas one might expect from the Rolandic tumors. The research indicates that reorganization of the finger motor representations might be limited along the middle-to-dorsal dimension of the dorsal premotor areas (posterior MFG and SFG) and might not cross rostrally from the primary motor cortex (PrG) to the dorsal premotor cortex.

Source: Study investigates plasticity of motor representations in patients with brain tumors

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[Abstract] The treatment of fatigue by non-invasive brain stimulation

Summary

The use of non-invasive brain neurostimulation (NIBS) techniques to treat neurological or psychiatric diseases is currently under development. Fatigue is a commonly observed symptom in the field of potentially treatable pathologies by NIBS, yet very little data has been published regarding its treatment. We conducted a review of the literature until the end of February 2017 to analyze all the studies that reported a clinical assessment of the effects of NIBS techniques on fatigue. We have limited our analysis to repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). We found only 15 studies on this subject, including 8 tDCS studies and 7 rTMS studies. Of the tDCS studies, 6 concerned patients with multiple sclerosis while 6 rTMS studies concerned fibromyalgia or chronic fatigue syndrome. The remaining 3 studies included patients with post-polio syndrome, Parkinson’s disease and amyotrophic lateral sclerosis. Three cortical regions were targeted: the primary sensorimotor cortex, the dorsolateral prefrontal cortex and the posterior parietal cortex. In all cases, tDCS protocols were performed according to a bipolar montage with the anode over the cortical target. On the other hand, rTMS protocols consisted of either high-frequency phasic stimulation or low-frequency tonic stimulation. The results available to date are still too few, partial and heterogeneous as to the methods applied, the clinical profile of the patients and the variables studied (different fatigue scores) in order to draw any conclusion. However, the effects obtained, especially in multiple sclerosis and fibromyalgia, are really carriers of therapeutic hope.

Source: The treatment of fatigue by non-invasive brain stimulation

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[Abstract] Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS) – Clinical Neurophysiology

Highlights

  • A group of European experts reviewed current evidence for therapeutic efficacy of tDCS.
  • Level B evidence (probable efficacy) was found for fibromyalgia, depression and craving.
  • The therapeutic relevance of tDCS needs to be further explored in these and other indications.

Abstract

A group of European experts was commissioned by the European Chapter of the International Federation of Clinical Neurophysiology to gather knowledge about the state of the art of the therapeutic use of transcranial direct current stimulation (tDCS) from studies published up until September 2016, regarding pain, Parkinson’s disease, other movement disorders, motor stroke, poststroke aphasia, multiple sclerosis, epilepsy, consciousness disorders, Alzheimer’s disease, tinnitus, depression, schizophrenia, and craving/addiction.

The evidence-based analysis included only studies based on repeated tDCS sessions with sham tDCS control procedure; 25 patients or more having received active treatment was required for Class I, while a lower number of 10–24 patients was accepted for Class II studies. Current evidence does not allow making any recommendation of Level A (definite efficacy) for any indication. Level B recommendation (probable efficacy) is proposed for: (i) anodal tDCS of the left primary motor cortex (M1) (with right orbitofrontal cathode) in fibromyalgia; (ii) anodal tDCS of the left dorsolateral prefrontal cortex (DLPFC) (with right orbitofrontal cathode) in major depressive episode without drug resistance; (iii) anodal tDCS of the right DLPFC (with left DLPFC cathode) in addiction/craving. Level C recommendation (possible efficacy) is proposed for anodal tDCS of the left M1 (or contralateral to pain side, with right orbitofrontal cathode) in chronic lower limb neuropathic pain secondary to spinal cord lesion. Conversely, Level B recommendation (probable inefficacy) is conferred on the absence of clinical effects of: (i) anodal tDCS of the left temporal cortex (with right orbitofrontal cathode) in tinnitus; (ii) anodal tDCS of the left DLPFC (with right orbitofrontal cathode) in drug-resistant major depressive episode.

It remains to be clarified whether the probable or possible therapeutic effects of tDCS are clinically meaningful and how to optimally perform tDCS in a therapeutic setting. In addition, the easy management and low cost of tDCS devices allow at home use by the patient, but this might raise ethical and legal concerns with regard to potential misuse or overuse. We must be careful to avoid inappropriate applications of this technique by ensuring rigorous training of the professionals and education of the patients.

Source: Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS) – Clinical Neurophysiology

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[WEB SITE] Scientists discover neuron-producing stem cells in the membranes covering the brain

Credit: Heidi Cartwright, Wellcome Images

 

Discovery brings with it possible implications for brain regeneration –

In a cross-domain study directed by professor Peter Carmeliet (VIB – KU Leuven), researchers discovered unexpected cells in the protective membranes that enclose the brain, the so called meninges. These ‘neural progenitors’ (stem cells that differentiate into different kinds of neurons) are produced during embryonic development.

See Also: Stem cells in the brain: Limited self-renewal

These findings show that the neural progenitors found in the meninges produce new neurons after birth, highlighting the importance of meningeal tissue as well as these cells’ potential in the development of new therapies for brain damage or neurodegeneration. A paper highlighting the results is published in the journal Cell Stem Cell.

Scientists’ understanding of brain plasticity, or the ability of the brain to grow, develop, recover from injuries and adapt to changing conditions throughout our lives, has been greatly broadened in recent years. Before the discoveries of the last few decades, neurologists once thought that the brain became ‘static’ after childhood. This dogma has changed, with researchers finding more and more evidence that the brain is capable of healing and regenerating in adulthood, thanks to the presence of stem cells. However, neuronal stem cells were generally believed to only reside within the brain tissue, not in the membranes surrounding it.

The meninges: unappreciated no more

Believed in the past to serve a mainly protective function to dampen mechanical shocks, the meninges have been historically underappreciated by science as having neurological importance in its own right. The data gathered by the team challenges the current idea that neural precursors—or stem cells that give rise to neurons—can only be found inside actual brain tissue.

Learn More: Scientists sniff out unexpected role for stem cells in the brain

Prof. Peter Carmeliet notes: “The neuronal stems cells that we discovered inside the meninges differentiate to full neurons, electrically-active and functionally integrated into the neuronal circuit. To show that the stem cells reside in the meninges, we used the extremely powerful single-cell RNA sequencing technique, a very novel top-notch technique, capable of identifying the [complex gene expression signature] nature of individual cells in a previously unsurpassed manner, a première at VIB.”

Following up on future research avenues

When it comes to future leads for this discovery, the scientists also see possibilities for translation into clinical application, though future work is required.

“An intriguing question is whether these neuronal stem cells in the meninges could lead to better therapies for brain damage or neurodegeneration. However, answering this question would require a better understanding of the molecular mechanisms that regulate the differentiation of these stem cells,” says Carmeliet. “How are these meningeal stem cells activated to become different kinds of neurons? Can we therapeutically ‘hijack’ their regeneration potential to restore dying neurons in, for example, Alzheimer’ Disease, Parkinson’s Disease, amyotrophic lateral sclerosis (ALS), and other neurodegenerative disorders? Also, can we isolate these neurogenic progenitors from the meninges at birth and use them for later transplantation? These findings open up very exciting research opportunities for the future.”

Moving into unchartered territory is high risk, and can offer high gain, but securing funding for such type of research is challenging. However, Carmeliet’s discoveries were made possible to a large extent by funding through “Opening the Future: pioneering without boundaries”, a recently created Mecenas Funding Campaign for funding of high risk brain research but with potential for breakthrough discoveries, started up by the KU Leuven in 2013 and unique in Flanders.

Read Next: A better way to grow motor neurons from stem cells

“Being able to use such non-conventional funding channels is of utmost importance to break new boundaries in research,” says Carmeliet. “This unique Mecenas funding initiative by the KU Leuven is innovative and boundary-breaking by itself. Our entire team is enormously grateful for the opportunities it has created for our investigations”.

Note: Material may have been edited for length and content. For further information, please contact the cited source.

VIB – Flanders Institute for Biotechnology   press release

Publication

Bifari F et al. Neurogenic Radial Glia-like Cells in Meninges Migrate and Differentiate into Functionally Integrated Neurons in the Neonatal Cortex.   Cell Stem Cell, Published Online November 23 2016. doi: 10.1016/j.stem.2016.10.020

Source: Scientists discover neuron-producing stem cells in the membranes covering the brain

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