Neuroscience

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Posts tagged neurological diseases

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Research gives unprecedented 3-D view of important brain receptor Researchers with Oregon Health & Science University’s Vollum Institute have given science a new and unprecedented 3-D view of one of the most important receptors in the brain — a receptor that allows us to learn and remember, and whose dysfunction is involved in a wide range of neurological diseases and conditions, including Alzheimer’s, Parkinson’s, schizophrenia and depression. The unprecedented view provided by the OHSU research, published online June 22 in the journal Nature, gives scientists new insight into how the receptor — called the NMDA receptor — is structured. And importantly, the new detailed view gives vital clues to developing drugs to combat the neurological diseases and conditions. "This is the most exciting moment of my career," said Eric Gouaux, a senior scientist at the Vollum Institute and a Howard Hughes Medical Institute investigator. "The NMDA receptor is one of the most essential, and still sometimes mysterious, receptors in our brain. Now, with this work, we can see it in fascinating detail." Receptors facilitate chemical and electrical signals between neurons in the brain, allowing those neurons to communicate with each other. The NMDA (N-methyl-D-aspartate) receptor is one of the most important brain receptors, as it facilitates neuron communication that is the foundation of memory, learning and thought. Malfunction of the NMDA receptor occurs when it is increasingly or decreasingly active and is associated with a wide range of neurological disorders and diseases. Alzheimer’s disease, Parkinson’s disease, depression, schizophrenia and epilepsy are, in many instances, linked to problems with NMDA activity. Scientists across the world study the NMDA receptor; some of the most notable discoveries about the receptor during the past three decades have been made by OHSU Vollum scientists. The NMDA receptor makeup includes receptor “subunits” — all of which have distinct properties and act in distinct ways in the brain, sometimes causing neurological problems. Prior to Gouaux’s study, scientists had only a limited view of how those subtypes were arranged in the NMDA receptor complex and how they interacted to carry out specific functions within the brain and central nervous system. Gouaux’s team of scientists – Chia-Hsueh Lee, Wei Lu, Jennifer Michel, April Goehring, Juan Du and Xianqiang Song – created a 3-D model of the NMDA receptor through a process called X-ray crystallography. This process throws x-ray beams at crystals of the receptor; a computer calibrates the makeup of the structure based on how those x-ray beams bounce off the crystals. The resulting 3-D model of the receptor, which looks something like a bouquet of flowers, shows where the receptor subunits are located, and gives unprecedented insight into their actions. "This new detailed view will be invaluable as we try to develop drugs that might work on specific subunits and therefore help fight or cure some of these neurological diseases and conditions," Gouaux said. "Seeing the structure in more detail can unlock some of its secrets — and may help a lot of people."

Research gives unprecedented 3-D view of important brain receptor

Researchers with Oregon Health & Science University’s Vollum Institute have given science a new and unprecedented 3-D view of one of the most important receptors in the brain — a receptor that allows us to learn and remember, and whose dysfunction is involved in a wide range of neurological diseases and conditions, including Alzheimer’s, Parkinson’s, schizophrenia and depression.

The unprecedented view provided by the OHSU research, published online June 22 in the journal Nature, gives scientists new insight into how the receptor — called the NMDA receptor — is structured. And importantly, the new detailed view gives vital clues to developing drugs to combat the neurological diseases and conditions.

"This is the most exciting moment of my career," said Eric Gouaux, a senior scientist at the Vollum Institute and a Howard Hughes Medical Institute investigator. "The NMDA receptor is one of the most essential, and still sometimes mysterious, receptors in our brain. Now, with this work, we can see it in fascinating detail."

Receptors facilitate chemical and electrical signals between neurons in the brain, allowing those neurons to communicate with each other. The NMDA (N-methyl-D-aspartate) receptor is one of the most important brain receptors, as it facilitates neuron communication that is the foundation of memory, learning and thought. Malfunction of the NMDA receptor occurs when it is increasingly or decreasingly active and is associated with a wide range of neurological disorders and diseases. Alzheimer’s disease, Parkinson’s disease, depression, schizophrenia and epilepsy are, in many instances, linked to problems with NMDA activity.

Scientists across the world study the NMDA receptor; some of the most notable discoveries about the receptor during the past three decades have been made by OHSU Vollum scientists.

The NMDA receptor makeup includes receptor “subunits” — all of which have distinct properties and act in distinct ways in the brain, sometimes causing neurological problems. Prior to Gouaux’s study, scientists had only a limited view of how those subtypes were arranged in the NMDA receptor complex and how they interacted to carry out specific functions within the brain and central nervous system.

Gouaux’s team of scientists – Chia-Hsueh Lee, Wei Lu, Jennifer Michel, April Goehring, Juan Du and Xianqiang Song – created a 3-D model of the NMDA receptor through a process called X-ray crystallography. This process throws x-ray beams at crystals of the receptor; a computer calibrates the makeup of the structure based on how those x-ray beams bounce off the crystals. The resulting 3-D model of the receptor, which looks something like a bouquet of flowers, shows where the receptor subunits are located, and gives unprecedented insight into their actions.

"This new detailed view will be invaluable as we try to develop drugs that might work on specific subunits and therefore help fight or cure some of these neurological diseases and conditions," Gouaux said. "Seeing the structure in more detail can unlock some of its secrets — and may help a lot of people."

Filed under NMDA receptor receptors neurological diseases x-ray crystallography neuroscience science

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Quantity, not just quality, in new Stanford brain scan method Researchers used magnetic resonance imaging to quantify brain tissue volume, a critical measurement of the progression of multiple sclerosis and other diseases. Imagine that your mechanic tells you that your brake pads seem thin, but doesn’t know how long they will last. Or that your doctor says your child has a temperature, but isn’t sure how high. Quantitative measurements help us make important decisions, especially in the doctor’s office. But a potent and popular diagnostic scan, magnetic resonance imaging (MRI), provides mostly qualitative information. An interdisciplinary Stanford team has now developed a new method for quantitatively measuring human brain tissue using MRI. The team members measured the volume of large molecules (macromolecules) within each cubic millimeter of the brain. Their method may change the way doctors diagnose and treat neurological diseases such as multiple sclerosis. "We’re moving from qualitative – saying something is off – to measuring how off it is," said Aviv Mezer, postdoctoral scholar in psychology. The team’s work, funded by research grants from the National Institutes of Health, appears in the journal Nature Medicine. Mezer, whose background is in biophysics, found inspiration in seemingly unrelated basic research from the 1980s. In theory, he read, magnetic resonance could quantitatively discriminate between different types of tissues. "Do the right modifications to make it applicable to humans," he said of adapting the previous work, "and you’ve got a new diagnostic." Previous quantitative MRI measurements required uncomfortably long scan times. Mezer and psychology Professor Brian Wandell unearthed a faster scanning technique, albeit one noted for its lack of consistency. "Now we’ve found a way to make the fast method reliable," Mezer said. Mezer and Wandell, working with neuroscientists, radiologists and chemical engineers, calibrated their method with a physical model – a radiological “phantom” – filled with agar gel and cholesterol to mimic brain tissue in MRI scans. The team used one of Stanford’s own MRI machines, located in the Center for Cognitive and Neurobiological Imaging, or CNI. Wandell directs the two-year-old center. Most psychologists, he said, don’t have that level of direct access to their MRI equipment. "Usually there are many people between you and the instrument itself," Wandell said. This study wouldn’t have happened, Mezer said, without the close proximity and open access to the instrumentation in the CNI. Their results provided a new way to look at a living brain. MRI images of the brain are made of many “voxels,” or three-dimensional elements. Each voxel represents the signal from a small volume of the brain, much like a pixel represents a small volume of an image. The fraction of each voxel filled with brain tissue (as opposed to water) is called the macromolecular tissue volume, or MTV. Different areas of the brain have different MTVs. Mezer found that his MRI method produced MTV values in agreement with measurements that, until now, could only come from post-mortem brain specimens. This is a useful first measurement, Mezer said. “The MTV is the most basic entity of the structure. It’s what the tissue is made of.” The team applied its method to a group of multiple sclerosis patients. MS attacks a layer of cells called the myelin sheath, which protects neurons the same way insulation protects a wire. Until now, doctors typically used qualitative MRI scans (displaying bright or dark lesions) or behavioral tests to assess the disease’s progression. Myelin comprises most of the volume of the brain’s “white matter,” the core of the brain. As MS erodes myelin, the MTV of the white matter changes. Just as predicted, Mezer and Wandell found that MS patients’ white matter tissue volumes were significantly lower than those of healthy volunteers. Mezer and colleagues at Stanford School of Medicine are now following up with the patients to evaluate the effect of MS drug therapies. They’re using MTV values to track individual brain tissue changes over time. The team’s results were consistent among five MRI machines. Mezer and Wandell will next use MRI measurements to monitor brain development in children, particularly as the children learn to read. Wandell’s previous work mapped the neural connections involved in learning to read. MRI scans can measure how those connections form. "You can compare whether the circuits are developing within specified limits for typical children," Wandell said, "or whether there are circuits that are wildly out of spec, and we ought to look into other ways to help the child learn to read." Tracking MTV, the team said, helps doctors better compare patients’ brains to the general population – or to their own history – giving them a chance to act before it’s too late.

Quantity, not just quality, in new Stanford brain scan method

Researchers used magnetic resonance imaging to quantify brain tissue volume, a critical measurement of the progression of multiple sclerosis and other diseases.

Imagine that your mechanic tells you that your brake pads seem thin, but doesn’t know how long they will last. Or that your doctor says your child has a temperature, but isn’t sure how high. Quantitative measurements help us make important decisions, especially in the doctor’s office. But a potent and popular diagnostic scan, magnetic resonance imaging (MRI), provides mostly qualitative information.

An interdisciplinary Stanford team has now developed a new method for quantitatively measuring human brain tissue using MRI. The team members measured the volume of large molecules (macromolecules) within each cubic millimeter of the brain. Their method may change the way doctors diagnose and treat neurological diseases such as multiple sclerosis.

"We’re moving from qualitative – saying something is off – to measuring how off it is," said Aviv Mezer, postdoctoral scholar in psychology. The team’s work, funded by research grants from the National Institutes of Health, appears in the journal Nature Medicine.

Mezer, whose background is in biophysics, found inspiration in seemingly unrelated basic research from the 1980s. In theory, he read, magnetic resonance could quantitatively discriminate between different types of tissues.

"Do the right modifications to make it applicable to humans," he said of adapting the previous work, "and you’ve got a new diagnostic."

Previous quantitative MRI measurements required uncomfortably long scan times. Mezer and psychology Professor Brian Wandell unearthed a faster scanning technique, albeit one noted for its lack of consistency.

"Now we’ve found a way to make the fast method reliable," Mezer said.

Mezer and Wandell, working with neuroscientists, radiologists and chemical engineers, calibrated their method with a physical model – a radiological “phantom” – filled with agar gel and cholesterol to mimic brain tissue in MRI scans.

The team used one of Stanford’s own MRI machines, located in the Center for Cognitive and Neurobiological Imaging, or CNI. Wandell directs the two-year-old center. Most psychologists, he said, don’t have that level of direct access to their MRI equipment.

"Usually there are many people between you and the instrument itself," Wandell said.

This study wouldn’t have happened, Mezer said, without the close proximity and open access to the instrumentation in the CNI.

Their results provided a new way to look at a living brain.

MRI images of the brain are made of many “voxels,” or three-dimensional elements. Each voxel represents the signal from a small volume of the brain, much like a pixel represents a small volume of an image. The fraction of each voxel filled with brain tissue (as opposed to water) is called the macromolecular tissue volume, or MTV. Different areas of the brain have different MTVs. Mezer found that his MRI method produced MTV values in agreement with measurements that, until now, could only come from post-mortem brain specimens.

This is a useful first measurement, Mezer said. “The MTV is the most basic entity of the structure. It’s what the tissue is made of.”

The team applied its method to a group of multiple sclerosis patients. MS attacks a layer of cells called the myelin sheath, which protects neurons the same way insulation protects a wire. Until now, doctors typically used qualitative MRI scans (displaying bright or dark lesions) or behavioral tests to assess the disease’s progression.

Myelin comprises most of the volume of the brain’s “white matter,” the core of the brain. As MS erodes myelin, the MTV of the white matter changes. Just as predicted, Mezer and Wandell found that MS patients’ white matter tissue volumes were significantly lower than those of healthy volunteers. Mezer and colleagues at Stanford School of Medicine are now following up with the patients to evaluate the effect of MS drug therapies. They’re using MTV values to track individual brain tissue changes over time.

The team’s results were consistent among five MRI machines.

Mezer and Wandell will next use MRI measurements to monitor brain development in children, particularly as the children learn to read. Wandell’s previous work mapped the neural connections involved in learning to read. MRI scans can measure how those connections form.

"You can compare whether the circuits are developing within specified limits for typical children," Wandell said, "or whether there are circuits that are wildly out of spec, and we ought to look into other ways to help the child learn to read."

Tracking MTV, the team said, helps doctors better compare patients’ brains to the general population – or to their own history – giving them a chance to act before it’s too late.

Filed under brain mapping MS myelin brain tissue neuroimaging neurological diseases neuroscience science

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Learning how the brain takes out its trash may help decode neurological diseases Imagine that garbage haulers don’t exist. Slowly, the trash accumulates in our offices, our homes, it clogs the streets and damages our cars, causes illness and renders normal life impossible. Garbage in the brain, in the form of dead cells, must also be removed before it accumulates, because it can cause both rare and common neurological diseases, such as Parkinson’s. Now, University of Michigan researchers are a leap closer to decoding the critical process of how the brain clears dead cells, said Haoxing Xu, associate professor in the U-M Department of Molecular, Cellular and Developmental Biology. A new U-M study identified two critical components of this cell clearing process: an essential calcium channel protein, TRPML1, that helps the so-called garbage collecting cells, called microphages or microglia, to clear out the dead cells; and alipid molecule, which helps activate TRPML1 and the process that allows the microphages to remove these dead cells. Moreover, the Xu lab identified a synthetic chemical compound that can activate TRPML1. Because this chemical compound ultimately helps activate this cell-clearing process, it provides a drug target that could help combat these neurological diseases. "This is clearly a drug target," Xu said. "What this paper picks out is exactly what is going wrong in this process." Scientists began by looking at a very rare neurodegenerative disease called Type IV Mucolipidosis, a childhood neurodegenerative disease characterized by multiple disabilities. Xu’s group found that lack of TRPML1 function, which is the channel through which calcium is released from the lysosome—the cell’s recycling center—into the microphage cells, contributes to these neurodegenerative conditions. If this calcium channel doesn’t work, calcium cannot be released, and dead cells aren’t removed, Xu said. The synthetic chemical compound stimulates the TRPML1 calcium channel to release the calcium into the cell. Further, dead cells “are bad for live cells,” Xu said. An excess of dead cells leads the macrophage cells to also kill healthy neurons necessary for neurological function, which in turn can lead to these neurodegenerative diseases. There are many neurodegenerative diseases, some very rare and some more common, such as Parkinson’s and ALS. The common thread among them is the dearth of live and functioning neurons, which prevents the neurological system from carrying out normal functions, Xu said. Thus, identifying a lipid molecule and also chemical compounds that stimulates proper function of the TRMPL1 function could revolutionize the treatment of these neurodegenerative diseases. The next step in Xu’s research is to test how these general observations are helpful to the neurological diseases and whether the compound is effective in animal models of neurological diseases. The paper, “A TRP channel in the lysosome regulates large particle phagocytosis via focal exocytosis,” appeared Aug. 29 online in Developmental Cell.

Learning how the brain takes out its trash may help decode neurological diseases

Imagine that garbage haulers don’t exist. Slowly, the trash accumulates in our offices, our homes, it clogs the streets and damages our cars, causes illness and renders normal life impossible.

Garbage in the brain, in the form of dead cells, must also be removed before it accumulates, because it can cause both rare and common neurological diseases, such as Parkinson’s. Now, University of Michigan researchers are a leap closer to decoding the critical process of how the brain clears dead cells, said Haoxing Xu, associate professor in the U-M Department of Molecular, Cellular and Developmental Biology.

A new U-M study identified two critical components of this cell clearing process: an essential calcium channel protein, TRPML1, that helps the so-called garbage collecting cells, called microphages or microglia, to clear out the dead cells; and alipid molecule, which helps activate TRPML1 and the process that allows the microphages to remove these dead cells.

Moreover, the Xu lab identified a synthetic chemical compound that can activate TRPML1. Because this chemical compound ultimately helps activate this cell-clearing process, it provides a drug target that could help combat these neurological diseases.

"This is clearly a drug target," Xu said. "What this paper picks out is exactly what is going wrong in this process."

Scientists began by looking at a very rare neurodegenerative disease called Type IV Mucolipidosis, a childhood neurodegenerative disease characterized by multiple disabilities.

Xu’s group found that lack of TRPML1 function, which is the channel through which calcium is released from the lysosome—the cell’s recycling center—into the microphage cells, contributes to these neurodegenerative conditions. If this calcium channel doesn’t work, calcium cannot be released, and dead cells aren’t removed, Xu said. The synthetic chemical compound stimulates the TRPML1 calcium channel to release the calcium into the cell.

Further, dead cells “are bad for live cells,” Xu said. An excess of dead cells leads the macrophage cells to also kill healthy neurons necessary for neurological function, which in turn can lead to these neurodegenerative diseases.

There are many neurodegenerative diseases, some very rare and some more common, such as Parkinson’s and ALS. The common thread among them is the dearth of live and functioning neurons, which prevents the neurological system from carrying out normal functions, Xu said.

Thus, identifying a lipid molecule and also chemical compounds that stimulates proper function of the TRMPL1 function could revolutionize the treatment of these neurodegenerative diseases.

The next step in Xu’s research is to test how these general observations are helpful to the neurological diseases and whether the compound is effective in animal models of neurological diseases.

The paper, “A TRP channel in the lysosome regulates large particle phagocytosis via focal exocytosis,” appeared Aug. 29 online in Developmental Cell.

Filed under neurological diseases microphages microglia calcium channel lysosome neuroscience science

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A new tool for brain research

Physicists and neuroscientists from The University of Nottingham and University of Birmingham have unlocked one of the mysteries of the human brain, thanks to new research using functional Magnetic Resonance Imaging (fMRI) and electroencephalography (EEG).

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The work will enable neuroscientists to map a kind of brain function that up to now could not be studied, allowing a more accurate exploration of how both healthy and diseased brains work.

Functional MRI is commonly used to study how the brain works, by providing spatial maps of where in the brain external stimuli, such as pictures and sounds, are processed. The fMRI scan does this by detecting indirect changes in the brain’s blood flow in response to changes in electrical signalling during the stimulus.

Combining techniques

A signal change that happens after the stimulus has stopped is also observed with the fMRI scan. This is called the post-stimulus signal and up until now it has not been used to study how the brain works because its origin was uncertain.

In novel experiments, the research team has now combined fMRI techniques with EEG, which measures electrical activity in the brain, to show that the post-stimulus signal also actually reflects changes in brain signalling.

18 healthy volunteers were monitored by using EEG to measure the electrical activity generated by their brains’ neurons (the signalling cells) while simultaneously recording fMRI measurements. A stimulus of electrical pulses was used to activate the part of the brain that controls movement in the right thumb.

The scientists then compared the EEG and fMRI signals and found that they both vary in the same way after the stimulus stops. This provides compelling evidence that the post-stimulus fMRI signal is a measure of neuronal activity rather than just changes in the brain’s blood flow. Curiously, the team also found the post-stimulus fMRI signal was not consistent, even though the stimulus input to the brain was the same each time. This natural variability in the brain response was also reflected by the EEG activity and the researchers suggest that this signal might help the brain make the transition from processing stimuli back to their internal thoughts in different ways.

New window

Dr Karen Mullinger from The University of Nottingham’s Sir Peter Mansfield Magnetic Resonance Centre said: “This work opens a new window of time in the fMRI signal in which we can look at what the brain is doing. It may also open up new research avenues in exploring the function of the healthy brain and the study of neurological diseases.”

Dr Stephen Mayhew from Birmingham University Imaging Centre said “We do not know what the exact role of the post-stimulus activity is or why this response is not always consistent when the stimulus input to the brain is the same. We have already secured funding through the Birmingham-Nottingham Strategic Collaboration Fund to continue this research into further understanding of human brain function using combinations of neuroimaging methods.”

Director of the Sir Peter Mansfield Magnetic Resonance Centre, Professor Peter Morris, said: “Functional magnetic resonance imaging is the main tool available to cognitive neuroscientists for the investigation of human brain function. The demonstration in this paper, that the secondary fMRI response (the post-stimulus undershoot) is not simply a passive blood flow response, but is directly related to synchronous neural activity, as measured with EEG, heralds an exciting new chapter in our understanding of the workings of the human mind.”

The work has been funded by the Medical Research Council (MRC), Engineering and Physical Science Research Council (EPSRC), The University of Nottingham Anne McLaren Fellowships and University of Birmingham Fellowship and is published in the Proceedings of the National Academy of Sciences (PNAS).

(Source: nottingham.ac.uk)

Filed under neuroimaging fMRI EEG brain function brain activity neurological diseases neuroscience science

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…treating neurological diseases and computers that see!

Some 165 million Europeans are likely to experience some form of brain-related disease during their life. As the population ages, Alzheimer’s and other neurodegenerative or age-related mental disorders are affecting more people and contributing to higher health costs. Finding better ways of preventing and treating brain diseases is therefore becoming urgent, and understanding how our brains work is important to keep our economies at the forefront of new information technologies and services. EU-funded research is answering these challenges.

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As mentioned in the first part of this article, this May the European Commission announced EUR 150 million of funding for 20 new ICT research projects expected to deliver new insights and innovations relating to traumatic brain injury, mental disorders, pain, epilepsy and paediatric conduct disorders.

The European Commissioner for Research, Innovation and Science, Máire Geoghegan-Quinn has said, ”Treating those affected (by brain-related disease) is already costing us EUR 1.5 million every minute […] Brain research could help alleviate the suffering of millions of patients and those that care for them. Unlocking the secrets of how the brain works could also open up a whole new universe of services and products for our economies.”

Treating neurological diseases

Stroke is the most common neurological disease to afflict people, causing cognitive problems - such as difficulties with attention, memory or language - or severe physical disability. The incidence increases with age, making it the most frequent cause of life-long impairment in adulthood.

These effects tend to increase patients” dependence on other people, and this lost autonomy can then lead to depression. The CONTRAST project seeks to bridge the gap between institutional rehabilitation and monitoring of the patient at home.

The project is developing an adaptive ”human-computer interface” (HCI) to improve cognitive functioning, offering training modules that improve the recovery of attention and memory. Patients will be able to go through an individually tailored rehabilitation process at home at the computer, while their doctor provides home-based training and monitors their progress from the clinic.

A third of stroke patients will experience long-term physiological or cognitive disabilities - preventing them from maintaining independent lives. COGWATCH aims to enhance the rehabilitation of stroke patients with symptoms of ”apraxia and action disorganisation syndrome” (AADS). Such patients retain their motor capabilities but commit cognitive errors during every-day goal-oriented tasks.

The project is developing intelligent tools and objects, portable and wearable devices, and ambient systems to provide personalised cognitive rehabilitation at home for stroke patients with AADS symptoms. By providing persistent feedback, the system will help to re-train patients on how to carry out the everyday activities they need to be independent.

Parkinson’s disease is another neurodegenerative disorder that is growing in incidence as our population ages - it particularly affects areas of the brain that are involved in movement control. The CUPID project aims to develop innovative, personalised rehabilitation at home for people with Parkinson”s disease, based on the patient”s needs.

The CUPID service will employ wearable sensors, audio biofeedback, virtual reality and external cueing to provide intensive motivating training that is suited to the patient and monitored remotely - decreasing the need for travel to a rehabilitation centre.

By the end of its first year, in December 2012, the project had designed the rehabilitation exercises and developed prototype virtual games for these exercises, as well as the telemedicine infrastructure needed for remote supervision.

Epilepsy is another common neurological disorder that, despite progress in treatment, is still incurable. Nowadays, pharmaceutical treatment can reduce or remove the symptoms, but this needs life-long continuous adjustment in order to be effective. The condition therefore requires monitoring of multiple parameters for accurate diagnosis, prediction, alerting and prevention, as well as treatment follow-up and presurgical evaluation.

The ARMOR project is designing a more holistic, personalised, medically efficient and economical monitoring system to analyse brain and body data from epilepsy patients. This portable system will provide more accurate diagnosis for individual patients, and allow better understanding and prediction of the time and type of their seizures - helping to give a warning and ensure the availability of medical assistance and advice if necessary.

Amputation of a limb is not just a traumatic physical experience. It can also lead to sensations - usually accompanied by pain - that seem to come from the missing body part, called a ”phantom limb”. The TIME project is developing an alternative treatment for phantom limb pain based on a new ”human-machine interface” (HMI) and selective, electrical stimulation of the peripheral nerves.

Using an implantable electrode placed inside the nerve, and electrical stimulators placed outside the body, the system will provide electrical micro stimulation to help reduce painful sensations - and may even have applications such as enabling amputees to sense virtual environments by touch.

Seeing things

The potential of such techniques doesn’t stop at monitoring, diagnosis and managing chronic conditions. The OPTONEURO project could ultimately help return functional sight to blind people.

”Optogenetics” is an exciting new gene therapy technique that makes nerve cells sensitive to particular colours of light. Simple pulses of intense light cause these photosensitised nerve cells to fire ”action potentials”, the carriers of information in the nervous system. To activate the nerve cells, however, the new therapy depends on high illumination densities - bright light shining on very small areas.

The OPTONEURO project therefore aims to develop the complementary optoelectronics needed to stimulate these photosensitised neurons. The system would be scalable for applications both in basic neuroscience research and in ”neuroprosthesis”. In particular, the optoelectronics should be used in a future optogenetic-optoelectronic retinal prosthesis - an artificial eye - for those blinded by the ”retinitis pigmentosa” disease.

The project requires a team of specialists in photonics, micro-optics and neurobiology to develop an array of ultra-bright electronically controlled micro-LEDs, which could also provide a new research tool for the neuroscience and neurotechnology community.

The SEEBETTER project is also looking to develop artificial vision prosthetics for the blind. Conventional image sensors have severe limitations, but ”silicon retina” vision sensors aim to mimic the biological retina”s information processing - computing both spatial and temporal aspects of the visual input. To date, these silicon retinas suffer from low quantum efficiency - meaning low light sensitivity - and an inability to combine both spatial and temporal processing on the same chip.

SEEBETTER’s team of experts - from biology and biophysics, as well as biomedical, electrical and semiconductor engineering - aim to use genetic and physiological techniques to understand better the function of the retina and model the retina’s vision processing. They will then design and build the first high-performance silicon retina, implemented on a single silicon wafer, specialised for both spatial and temporal visual processing.

Understand the neurobiological principles of seeing - beyond the functioning of the retina alone - may help us to replicate the success of human vision for computers and robots. The RENVISION project aims to achieve a comprehensive understanding of how the retina encodes visual information through the different cellular layers and to use such insights to develop a retina-inspired computational approach to computer vision.

Using high-resolution 3D microscopy will allow the researchers to make images of the inner retinal layers at near-cellular resolution. This new knowledge on retinal processing will help develop advanced pattern recognition and machine-learning technologies. The project could therefore solve some of the most difficult tasks in computer vision - such as automated scene categorisation and human action recognition - so that robots and computers can see and perceive what is happening in the images they receive.

These are just some of the EU-funded ICT projects using electronics and computing technologies to understand, augment and improve the human brain and its functioning. The results have the potential to reduce the impact of disability and disease, and improve our computing power, IT infrastructure and economy.

Filed under neurological diseases cognitive functioning brain research optogenetics neuroscience science

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Research opens up possibility of therapies to restore blood-brain barrier

Research led by Queen Mary, University of London, has opened up the possibility that drug therapies may one day be able to restore the integrity of the blood-brain barrier, potentially slowing or even reversing the progression of diseases like multiple sclerosis (MS). The study, funded by the Wellcome Trust, is published in Proceedings of the National Academy of Sciences.

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The blood-brain barrier (BBB) is a layer of cells, including endothelial cells, which line the blood vessels in the brain and spinal cord. These cells act as a barrier, stopping certain molecules, including immune cells and viruses, passing from the blood stream into the central nervous system (brain and spinal cord).

In a number of neurodegenerative brain diseases, including MS, the BBB is compromised, allowing inappropriate cells to pass into the brain with devastating consequences.

In this study the researchers identified a specific protein – known as Annexin A1 (ANXA1) – as being integral in maintaining the BBB in the brain. The authors initially found that mice bred to lack this protein showed a decrease in integrity of the BBB compared to controls.

Taking this finding, they then investigated the potential role of ANXA1 in conditions which involve progressive breakdown of the BBB, including MS and Parkinson’s disease, by examining post-mortem human brain tissue samples. ANXA1 was present in the cells of samples from individuals who did not have a neurological disease and also in samples from patients who had died with Parkinson’s disease. However, it was not detectable in the endothelial cells in samples from patients who had died with MS.

Crucially, the researchers found that treating in vitro brain endothelial cells with human recombinant ANXA1 restored the key cellular features needed to reinstate the integrity of the BBB. The same was seen with the ANXA1 knockout mice, where administering the protein reversed the permeability of the BBB within 24 hours.

Dr Egle Solito, from Barts and The London School of Medicine and Dentistry, part of Queen Mary, who co-ordinated the study said: “Our findings suggest this protein plays a key role in maintaining a functioning BBB and, more importantly, has the potential to rescue defects in the BBB. We now need to carry on our research to see how much this molecule may be exploited for therapeutic uses in conditions such as MS, or as a biomarker to help in early diagnosis.”

(Source: qmul.ac.uk)

Filed under brain cells CNS blood–brain barrier neurological diseases science

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