Posts Tagged brain
Neurodevelopment is an incredibly complex, but tightly controlled process governed by the sequential action of various genes. Neurodevelopment continues well after birth into early adolescence. Impairments to neurodevelopment at any stage can give rise to neurodevelopmental disorders.
Neural Tube & Early Brain Structures
At the very beginning of embryogenesis, 3 germ layers develop; the ectoderm, mesoderm, and endoderm. The ectoderm gives rise to the brain and skin (epidermis) and lies on top of the developing embryo’s mesoderm which gives rise to skeletal muscle, blood vessels, dermis, and connective tissues. The endoderm is the bottom layer that gives rise to the gut, respiratory epithelia, and many of the body’s other organs.
The brain starts as a simple sheet of ectodermal cells called the neural plate around the end of the 2nd week of embryogenesis (on day 13; E13). Immediately below the neural plate, a group of mesodermal cells form the notochord – present in all vertebrates. The notochord is what initially causes the folding in of the neural plate (neural groove) causing the ends of the neural plate to fuse together forming the neural tube between E20-27. The remaining ectodermal tissue will give rise to epidermal tissues and neural crest cells give rise to many other types of tissue.
The top of the neural tube is covered by a surface ectoderm which has a high expression of BMP & Wnt signaling causing the top of the neural tube to become the roof plate. The bottom of the neural tube is in close proximity to the notochord which has a high expression level of Shh giving rise to the floor plate in the neural tube. This early genetic patterning is what gives rise to the earliest structural organization of the developing brain where the top (dorsal) will give rise to sensory neurons, and the bottom (ventral) will give rise to motor neurons.
The neural tube gives rise to a rapidly developing 3D structure of the early brain that grows almost 10x fold in size from 3-5mm (E27) to 27-31mm by week 8. By this stage, anterior-posterior aspects of the developing brain are well defined by the presence of 3 brain “pouches”: the prosencephalon anteriorly (will give rise to the forebrain), the mesencephalon in the middle which will give rise to the midbrain, and the rhombencephalon posteriorly which will give rise to the hindbrain.
As the embryo continues to develop, the prosencephalon further divides into telencephalon (cerebrum; neocortex) and diencephalon (thalamus/hypothalamus), and the rhombencephalon divides into the metencephalon (pons/cerebellum) and myelencephalon (medulla). These processes are governed by differential gene expression and each of these newly formed areas continues to expand as neurons and glia begin to populate them.
Cortical and Neuronal Development
The neocortex develops from the telencephalon in the developing brain. Anterior-posterior regional patterning is governed by the genetic expression of different transcription factors and regulatory genes. For example, Pax6 and Emx2 are expressed in opposing gradients along with anterior-posterior cortex with Emx2 being highly expressed posterior to medial regions and lowest in anterior regions (in a gradient) whereas Pax6 has the opposite gradient. The highest levels of Emx2 (little Pax6) give rise to the visual cortex (V1). Medium levels of both Emx2 and Pax6 along the middle give rise to the somatosensory cortex (S1). High levels of Pax6 (little Emx2) give rise to the motor cortex (M1).
A key feature of some higher-order mammals (e.g., humans, elephants, dogs, non-human primates, and whales) is the presence of folds (grooves and ridges) on the brain surface called gyri and sulci which massively increase the surface area and volume of the brain. The presence of these on a brain is known as gyrencephalic, whereas the lack of gyri and sulci is lissecephalic – for example, rodent brains. These first begin to emerge around gestation week 8 (GW8) with the first of these being the longitudinal fissure which separates the 2 hemispheres of the brain (finishing at GW22). Other primary sulci form around GW14-26 with secondary and tertiary sulci continuing to form GW30-36.
Neurons begin to form on E42 that will reside in the different regions of the whole brain including within the different layers of the neocortex (discussed below). Before E42, from E25-E42, neuronal progenitor cells symmetrically divide in their masses massively increasing the number of mitotic progenitors (dividing).
From E42, however, these cells begin to divide asymmetrically to give rise to 1 neuron which are post-mitotic cells, and 1 progenitor that can continually divide in this fashion. Neurons begin to migrate out of the proliferative zone (ventricular zone; VZ) into the developing cortex. Cortical neurogenesis is usually completed by around E108 in humans giving rise to the vast majority of adult neurons being present from birth.
- Research provides vital insights about excess coffee consumption and brain health
- Brain’s locus coeruleus may be a sophisticated regulator of learning and behavior
- Research shows how brain mechanisms of fatigue influence people’s motivation to work
Cortical neurogenesis is a very complex process and will be very briefly described in this article for simplicity. This is an incredibly important process that allows the highest order executive and cognitive functions which makes humans “human”. The adult cortex has 6 distinct layers which all have different neuronal populations residing in them. Initially, the first set of developing neurons remain the deepest (except the very first wave of neurons which go right to the periphery) whereas subsequent neurons move outwards in the developing cortex thus forming an “inside-out” pattern.
The very first neurons form and migrate from the ventricular zone (VZ) forming the preplate (PP). The next wave of neurons split the PP into the marginal zone (MZ) and the subplate (SP) which only remain for a short time. Many of these neurons use early scaffolding created by radial glial cells to migrate outwards. The intermediate zone (IZ) between the SZ and SP becomes a mature white matter layer. The cortical plate (CP) develops between the SP and MZ. In the adult brain, none of these embryonic structures remain, but 6 distinct layers remain populated with a plethora of different neuronal types e.g., corticofugal neurons in layers V and VI that project to subcortical areas whereas neurons in layers II-IV are predominantly intracortical neurons which are excitatory glutamatergic neurons.
It is also important to note that gliogenesis and myelination also occur in addition to axonal and synaptic formation – and synaptic changes occur throughout life. Glia cells (https://www.news-medical.net/health/The-Other-Brain-Cells-New-Insights-into-What-Glial-Cells-Do.aspx) (which make up most of the brain) arise from the early multipotent progenitors that give rise to neurons initially, then switching to glia later in embryogenesis (around week 24) after the first set of neurons have formed. An intricate network of blood vessels also begins to form within the brain and the cortical surface as the brain develops.
Whilst most brains (especially cortices) develop normally according to the tightly controlled sequential manner described above, there may be rare cases where the brain does not develop as planned due to a variety of reasons. These could be due to genetic and environmental factors such as alcohol and drug misuse during pregnancy. Consequently, a variety of different neurodevelopmental disorders can develop with clinical features ranging from barely noticeable (mildest pathology) to severely debilitating both mentally and physically (most severe). Some of these can be apparent from birth or in young infants, others develop later in life such as schizophrenia.
Some key neurodevelopmental disorders include:
- Angelman Syndrome – monogenic postnatal microcephaly caused by loss of function mutations in the maternally inherited UBE3A allele. Angelman syndrome is characterized by severe intellectual disability, absent speech, seizures, developmental delay, and a personality that has a “happy demeanor”.
- Rett Syndrome – monogenic postnatal microcephaly caused by loss of function mutations in the X-linked MECP2 gene (though also associated with CDKL5 & FOXG1). Rett syndrome is characterized by a typical early development, however, this is regressed with the loss of acquired skills, language, intellectual, and motor abilities.
- Autistic Spectrum Disorder (ASD) – a complex genetically and clinically heterogeneous disorder (with causes still not yet fully understood) caused by a variety of genetic interactions/multiple pathways. ASD is characterized by impaired communication and social interactions with some stereotyped behaviors.
- Schizophrenia – another complex disorder with causes still not fully understood though key genetic and environmental triggers are known to be involved. Schizophrenia can develop at any stage in life (not necessarily present from birth unlike the other disorders) and is characterized by positive symptoms (hallucinations and delusions) as well as negative symptoms (blunted affect and lack of motivation).
In summary, the human brain develops in a tightly controlled manner that begins as a simple tube of cells around the 3rd week of gestation. Intricate and complex cellular and molecular signaling pathways give rise to the multitude of complex cell types and cytoarchitecture (including the cortex) of the brain arising from early defined coordinates. The human brain expands massively within the developing cortex by the gyrification of the brain.
Whilst neuronal development is largely completed during embryogenesis, the brain continues to develop well into early adulthood. Abnormal brain development can lead to the onset of neurodevelopmental disorders which are usually present from birth or predispose individuals to neuropsychiatric conditions later in life.
- Jiang & Nardelli, 2016. Cellular and molecular introduction to brain development. Neurobiol Dis. 92(Pt A):3-17. https://pubmed.ncbi.nlm.nih.gov/26184894/
- Vasung et al, 2019. Exploring early human brain development with structural and physiological neuroimaging. Neuroimage. 187:226-254. https://pubmed.ncbi.nlm.nih.gov/30041061/
- Stiles & Jernigan, 2010. The basics of brain development. Neuropsychol Rev. 20(4):327-48. https://pubmed.ncbi.nlm.nih.gov/21042938/
WRITTEN BY: Carmen Leitch
We now know that COVID-19 can cause a range of problems in the brain. Some of these problems are taking months to clear up in patients, or they are still lingering. They may be on the milder side, like disruptions in the ability to sense smells or tastes, or they may be far more severe, with some patients complaining of memory problems and brain fog. Researchers have been trying to learn exactly how these symptoms are arising; for example, is the virus infecting the brain directly? Or is the brain impacted in a secondary way?
The blood-brain barrier seems to do a pretty good job of protecting the brain from the SARS-CoV-2 virus; viral levels seem to be very low in infected individuals. However, the virus can get into cells that make up the olfactory epithelium, a border that lines the nasal cavity and is also very close to the brain. The virus may be able to infect cells in the brain called astrocytes, which have a variety of roles. Astrocytes were once thought to work primarily to support neurons, but research has indicated that have other functions as well.
A recent preprint, not yet peer-reviewed, has suggested that SARS-CoV-2 can infect astrocytes in brain organoids, which are small, miniature models of human brains. Preliminary work by researchers in Brazil proposed that five people out of a group of 26 who had died from COVID-19 had evidence of SARS-CoV-2 infection in their brain cells; 66 percent of the infected cells in these patients were astrocytes. Another report compared gene expression in patients that had died of SARS-CoV-2 to controls, and determined that gene expression in astrocytes was disrupted even though the virus was not found there.
There may be no simple answer to the question of how many brain cells have to be infected for a problem to occur, Arnold Kriegstein, a neurologist at the University of California, San Francisco and a co-author on the organoid study told Nature. He explained that damaged cells in some regions of the brain might cause more problems than others.
There may also be another way that the virus causes neurological symptoms. Since the early days of the pandemic, clinicians and researchers noticed unusual blood clots in patients. Blood flow to the brain might be disrupted in some COVID-19 patients. Capillaries, which are vessels that move blood to small places in the body, also contain a type of cell called pericytes. According to a pre-print, SARS-CoV-2 can infect pericytes, and pericyte-like brain cells.
Another possibility is that the immune system overreaction induced by COVID-19 is also battering the brain. Some people generate autoantibodies, which attack their own cells, during the course of a serious infection. There is evidence that suggests these autoantibodies can pass through the blood brain barrier and play a role in neurodegenerative disorders.
Researchers are now working to earn more about autoantibodies in COVID-19 patients. One study has found that eleven of these critically ill patients all carried autoantibodies that could attach to neurons.
Treating these problems may be very complicated; clinicians might have to determine which mechanism is most likely causing a patient’s problems, or researchers may have to focus on creating a treatment that targets the one that’s most common.
A brand new stroke rehabilitation pattern that could improve the treatment effect of stroke survivors.
A stroke occurs when the part of the brain loses its blood supply and stops working. Stroke is the leading cause of death and disability in the adult population. 75% of the surviving patients will lose the ability to move independently.
Traditional stroke rehabilitation equipment allows patients to follow the movements of the equipment latently. Henceforth, the rehabilitation effect is poor, and the patient’s willingness to train is likewise low.
Now, Tongji Hospital and BrainCo have introduced NCyborg Project, a new stroke rehabilitation pattern based on brain-computer interface (BCI) and brain-inspired intelligent robots. The project will mainly focus on:
- An algorithm for analyzing the movement intention of stroke patients based on brain-machine interface technology.
- A motion control strategy for a rehabilitation robot based on brain-inspired motion perception.
- The mechanism of stroke rehabilitation using brain-inspired intelligent robots.
The main aim of the NCyborg Project is to develop an easy-to-use, reliable and affordable stroke rehabilitation robot to improve the rehabilitation effect of stroke survivors, speed up the rehabilitation process, and reduce the costs.
The organization will start training the robot to support the rehabilitation of the hand. The robot is expected to recognize no less than eight hand movement intentions with a recognition accuracy of ≥ 90% and a response time ≤ of 300 ms.
Co-corresponding author, Jonh H. Zhang, explains: “The project’s goal is to develop an easy-to-use, reliable and affordable stroke rehabilitation robot that will improve the effect of rehabilitation for stroke survivors, speed up the rehabilitation process, and reduce the costs involved.”
Co-corresponding author, Bicheng Han, adds: “We hope that, within five years, millions of stroke patients will be using this product and see their lives improve.”
Co-corresponding author Zhouping Tang said, “the ‘N’ in the NCyborg Project name stands for ‘neural,’ while in fictional stories ‘cyborg’ is often an icon that is enhanced mentally and/or physically over and above the ‘norm’ with technology. In the real world, we believe that NCyborg Project will set up a brand-new stroke rehabilitation pattern which could qualitatively improve the treatment effect for stroke survivors.”
- Qi Huang et al. NCyborg Project – A new stroke rehabilitation pattern based on brain-computer interface. DOI: 10.1016/j.hest.2021.05.002
Focus, Concentration, Improve, Recharge, Reading, Studying Music
Reviewed by Emily Henderson, B.Sc. May 4 2021
Repetitive transcranial magnetic stimulation, or rTMS, was FDA approved in 2008 as a safe and effective noninvasive treatment for severe depression resistant to antidepressant medications. A small coil positioned near the scalp generates repetitive, pulsed magnetic waves that pass through the skull and stimulate brain cells to relieve symptoms of depression. The procedure has few side effects and is typically prescribed as an alternative or supplemental therapy when multiple antidepressant medications and/or psychotherapy do not work.
Despite increased use of rTMS in psychiatry, the rates at which patients respond to therapy and experience remission of often-disabling symptoms have been modest at best.
Now, for the first time, a team of University of South Florida psychiatrists and biomedical engineers applied an emerging functional neuroimaging technology, known as diffuse optical tomography (DOT), to better understand how rTMS works so they can begin to improve the technique’s effectiveness in treating depression. DOT uses near-infrared light waves and sophisticated algorithms (computer instructions) to produce three-dimensional images of soft tissue, including brain tissue.
Comparing depressed and healthy individuals, the USF researchers demonstrated that this newer optical imaging technique can safely and reliably measure changes in brain activity induced during rTMS in a targeted region of the brain implicated in mood regulation. Their findings were published April 1 in the Nature journal Scientific Reports.
This study is a good example of how collaboration between disciplines can advance our overall understanding of how a treatment like TMS works. We want to use what we learned from the application of the diffuse optical tomography device to optimize TMS, so that the treatments become more personalized and lead to more remission of depression.”
Shixie Jiang, MD, study lead author, third-year psychiatry resident, USF Health Morsani College of Medicine
DOT has been used clinically for imaging epilepsy, breast cancer, and osteoarthritis and to visualize activation of cortical brain regions, but the USF team is the first to introduce the technology to psychiatry to study brain stimulation with TMS.
“Diffuse optical tomography is really the only modality that can image brain function at the same time that TMS is administered,” said study principal investigator Huabei Jiang, PhD, a professor in the Department of Medical Engineering and father of Shixie Jiang. The DOT imaging system used for USF’s collaborative study was custom built in his laboratory at the USF College of Engineering.
The researchers point to three main reasons why TMS likely has not lived up to its full potential in treating major depression: nonoptimized brain stimulation targeting; unclear treatment parameters (i.e., rTMS dose, magnetic pulse patterns and frequencies, rest periods between stimulation intervals), and incomplete knowledge of how nerve cells in the brain respond physiologically to the procedure.
- Cardiovascular risk factors accumulated from childhood linked to poorer brain function at midlife
- Covid-19 patients show reduced gray matter volume in the brain
- New imaging technique captures real-time brain motion in stunning detail
Portable, less expensive, and less confining than some other neuroimaging equipment like MRIs, DOT still renders relatively high-resolution, localized 3D images. More importantly, Dr. Huabei Jiang said, DOT can be used during TMS without interfering with treatment’s magnetic pulses and without compromising the images and other data generated.
DOT relies on the fact that higher levels of oxygenated blood correlate with more brain activity and increased cerebral blood flow, and lower levels indicate less activity and blood flow. Certain neuroimaging studies have also revealed that depressed people display abnormally low brain activity in the prefrontal cortex, a brain region associated with emotional responses and mood regulation.
By measuring changes in near-infrared light, DOT detects changes in brain activity and, secondarily, changes in blood volume (flow) that might be triggering activation in the prefrontal cortex. In particular, the device can monitor altered levels of oxygenated, deoxygenated, and total hemoglobin, a protein in red blood cells carrying oxygen to tissues.
The USF study analyzed data collected from 13 adults (7 depressed and 6 healthy controls) who underwent DOT imaging simultaneously with rTMS at the USF Health outpatient psychiatry clinic. Applying the standard rTMS protocol, the treatment was aimed at the brain’s left dorsolateral prefrontal cortex – the region most targeted for depression.
The researchers found that the depressed patients had significantly less brain activation in response to rTMS than the healthy study participants. Furthermore, peak brain activation took longer to reach in the depressed group, compared to the healthy control group.
This delayed, less robust activation suggests that rTMS as currently administered under FDA guidelines may not be adequate for some patients with severe depression, Dr. Shixie Jiang said. The dose and timing of treatment may need to be adjusted for patients who exhibit weakened responses to brain stimulation at baseline (initial treatment), he added.
Larger clinical trials are needed to validate the USF preliminary study results, as well as to develop ideal treatment parameters and identify other dysfunctional regions in the depression-affected brain that may benefit from targeted stimulation.
“More work is needed,” Dr. Shixie Jiang said, “but advances in neuroimaging with new approaches like diffuse optical tomography hold great promise for helping us improve rTMS and depression outcomes.”
Reviewed by Emily Henderson, B.Sc. Feb 20 2021
Epilepsy is one of the most common neurological disorders, affecting over 50 Million people worldwide. Patients suffer from seizures caused by sudden neuronal activity engaging at times large networks of the brain. In a third of all cases the disease is resistant to drugs. The most common treatment option for these patients is surgical removal of the “epileptogenic zone”, the areas of the brain, where the seizures emerge.
“Surgery success depends on locating these areas as precisely as possible. But in clinical practice, this often proves very difficult, and the average surgery success rate remains at only around 60%”, says Viktor Jirsa. Any improvement would have major impact for many patients”.
The scientist has developed a computational tool, called “The Virtual Brain” (TVB), to model and predict activity in an individual patient brain. In collaboration with the neurologist Fabrice Bartolomei, they adapted the model to epilepsy, simulating the spread of individual seizure activity. The model thus can become an additional advisory tool for neurosurgeons to help target surgeries more precisely.
A clinical trial is currently underway to evaluate the personalized brain models of TVB as a new tool for epilepsy surgery planning, with promising first results. It is important to underscore that the Virtual Brain tool is still at clinical investigating stage and is therefore not yet available to patients.
The team now works on the next generation of The Virtual Brain, which boosts the accuracy of the model further using the EBRAINS research infrastructure. The objective is to significantly scale up the potential for personalized brain representation with the help of large brain data sets from the EBRAINS Brain Atlas. This includes the most detailed 3D representation of the brain’s anatomy, the BigBrain, at a resolution of 20 micrometers.
“Only EBRAINS allows to go to this massive scale and resolution”, Jirsa says. “Here brain data resources are made compatible and integrated with high-performance computing and informatics tools. EBRAINS enables the application of deep learning and other methods to find the configuration that most closely matches the patient’s own recordings of brain dynamics. This is an important step towards pinpointing the epileptogenic zone with greater precision.”
Katrin Amunts, Scientific Research Director of the HBP says: “The HBP’s multidisciplinary approach, gaining neuroscientific insight from the analysis of big data and neuroimaging studies, supported by brain modeling and advanced computing is a highly impactful way to advance brain research and bring innovation to patients and society.”
Pawel Swieboda, CEO of EBRAINS and Director General of the HBP, comments: “Prof Jirsa’s Virtual Brain computing tool is one of the many breakthrough achievements resulting from the cutting-edge scientific expertise of the Human Brain Project scientists and from the state-of-the art research infrastructure EBRAINS. We’re looking forward to sharing more brain health advances enabled by EBRAINS in the future. Meanwhile we invite researchers in different fields, such as neuroscience, neuroengineering, or neurotechnology – to list a few – to explore how the EBRAINS platform can enhance their own research.”
Source: Human Brain Project
During Autumn 2020, EFNA ran a competition on the theme ‘Me and my brain’. The public were invited to create a drawing, painting, collage or digital illustration representing their relationship with their brain, through artwork that explores their hopes, frustrations, or the day to day impact a neurological disorder has on their life.
83 artworks were received from across Europe. The standard, as you will see, was incredibly high. Our judges were extremely impressed by the artistic skill demonstrated and also moved by the meaningful nature of the works and their accompanying stories.
We are pleased today to announce the winners (one overall winner and four runners up).
First place winner:
|‘Marshmallow Head’Stacy Hart|
United Kingdom“Apart from extreme exhaustion that hits like a torpedo, Just one of the many symptoms of the complex debilitating condition known as M.E (Myalgic encephalomyelitis) Is cognitive impairment. It often feels like my brain is a wall of marshmallow and the thoughts that I have and the words I want to speak are somewhere right at the back behind it all and they are all jumbled and to process them more clearly so that I can verbalise them I have to try and get them to the front which requires trying to squeeze them through this thick spongy blob. Sometimes it works… and other times they still come through jumbled.”
|‘Cityscape III, Canary Wharf’Debbie Ayles|
United Kingdom“For many years I suffered terrible basilar migraines which totally disrupted my life. As well as headaches and sickness I experienced fragmentation of vision, twinkling, pulsing of colours and shapes, overlaying of images and my vision becoming two dimensional or ‘flattened’. I didn’t understand anything about aura.
Through a series of chance opportunities I met researchers in visual disturbance and learnt more about them and their impact on my artwork. In fact I was told my paintings displayed migraine aura many years before I began to experience migraine. I discovered my choice and distribution of colours were actually causing photosensitivity and break-through migraines on top of hormonal ones. I didn’t realise that I was painting the ‘twinkling, pulsing’ aura effect in my work. I was fortunate to collaborate with experts in ‘migraine art’ and discover how I could paint, use the colours I love and not trigger migraines.
I usually just have aura but am mindful of not using particular colours or patterns in a structured or linear way. The fragmentation of the picture plane and the ‘flatness’ continues in my work as it now illustrates that fleeting glimpse of something – when only bits of a view are logged by the brain and it ‘re-constructs’ the missing elements.
I have used architecture from the start, initially buildings supported by scaffolding. Unconsciously at first I began to realise these were a metaphor for the support network that surrounded me during those dreadful times.
Networks and grids are still dominant in my work, created by focusing on isolating the shapes of office or apartment windows for example, symbolising the little worlds where people work or live which can be lonely and dislocated from the outside world. Just like the experience of suffering migraine alone or retreating from the world until they have passed.
My artwork is primarily created as an object of enjoyment, a visual escape, a puzzle to explore or a chance for contemplation.
‘Cityscape III Canary Wharf’ was one of the first I painted after migraines reduced and I was able to enjoy the world of colour again.”
|‘Lost in my head’Danielle Sysmans|
Belgium“Hello, my name is Danielle and I live in Belgium.
I have had MS for many years. Decreased cognition is one of my main symptoms. MS is different for everyone. For me, next to my cognition problems I also have difficulty walking. Sometimes I can’t find the right words, I also forget a lot. My brain feels like a maze in which I continuously am searching for the right direction.
I’M LOST IN MY HEAD.”
|‘In water I am free’Melanie Hobday|
United Kingdom“I’ve had cervical dystonia for 24 years and I have been a regular swimmer for most of those years. I find swimming helps me to manage my dystonia by strengthening and balancing my muscles. It is retraining for my brain. In the water I feel free, I move through it slowly and as effortlessly as possible, mindful of the rhythm of my breath and the flow of my movements.”
Romania“Hi, my name is Ioana and I am a MS patient. I have created a medtech/ digital health solution for ms patients MSing with Trauma (https://msingwithtrauma.wixsite.com/home) , that converts MRI images of invisible disease into therapeutic music compositions. Designed for MS patients to have neurological and psychological effects. This project was born out of my love of technology, art and music.
‘Scattered’ is about when you piece yourself together after a ms attack.”
Congratulations to each of these fantastic winners!
And thank you to all those who entered. This was a close contest and we appreciate all of your work. A gallery of all the competition entries can be found here: https://www.efna.net/brainlifegoals/art-gallery/
Thank you also to our judging panel – Richard Roche, Alexandra Heumber Perry, Joanna Kniaz-Hawrot and Elizabeth Cunningham.
Alongside this art competition, EFNA ran a colouring competition for children. Congratulations to our winner, Szofia Dianis (age 6) from Hungary. Her entry is shown below. Congratulations also to the runners-up: Oliver Hokkanen (age 7, Finland), Rose Tobin Nnabuife (age 6, Ireland), Philip McCoy (age 7, Ireland) and Mustafa Bhatty (age 6, United Kingdom). Your prizes are on their way!
All entries to the colouring competition can be seen here.
[WEB PAGE] Plug n’ play brain stimulators will bring hi-tech depression treatment to the masses – European Commission
Depression affects a growing number of people each year, but current treatments either lack efficacy or aren’t personalised enough. PLATOSCIENCE has developed a brain stimulation device that could bring efficient treatment to people across Europe and around the world.
Over 300 million around the world are currently affected by depression. This number grew nearly 20 % between 2005 and 2015. In Europe, around 7 % of the population go through a major depressive experience, and around a quarter have trouble with anxiety-related issues.
Yet current treatment methods are either inefficient, or not personalised enough to individual patients. One promising option is to seize upon science’s growing understanding of brain stimulation. A Horizon 2020-funded project, PLATOSCIENCE, has been developing a technology that uses tDCS, essentially electrical stimulation for the brain, that works to excite or calm areas of the brain as a form of treatment.
PLATOSCIENCE has created the first plug n’ play brain stimulating headset for personalised at-home treatment of depression. “What’s really unique about this project is that the headset we are building both measures and stimulates brain activity. This means that the headset can analyse a depressed patient’s brain activity and then calculate the most effective treatment, followed by real time adjustments based on how the patient’s brain responds to the treatment,” explains Morten Friis-Olivarius, Founder and Scientific Director of PlatoScience ApS, and project coordinator.
The device, PlatoCure, uses three fixed, programmable electrodes built into an adjustable headset that can be configured for each patient’s head. “The headset stimulates the left and right side of an area in the frontal part of the brain named the dorsolateral prefrontal cortex and one area in the back, the precuneus,” says Friis-Olivarius.
The patent-protected device is linked to an app, which also collects data that can be used by health practitioners and psychotherapists, and which provides predictive analysis to fine tune treatment programmes. PlatoCure can also image scan the brain, using a common electrode-based technique known as electroencephalogram (EEG), which measures the brain during stimulation.
“Depression is typically associated with lower brain activity in certain areas of the brain. PlatoCure works by increasing spontaneous brain activity and metabolism in the areas that it identifies as underactive in a depressed patient,” Friis-Olivarius explains.
Over 4 000 peer-reviewed studies on the safety and efficacy of tDCS have been carried out. “The positive effects in depression treatment are well established,” says Friis-Olivarius. The PLATOSCIENCE team are currently preparing for a phase II application, and if successful will proceed with their own clinical trials.
The team found it unexpectedly challenging to separate the EEG signals from the tDCS stimulation, due to an extremely high signal-to-noise ratio. “We solved this with state-of-the-art signal-processing algorithms developed in collaboration with the Danish Technical University,” says Friis-Olivarius.
Stimulation for the masses
“During this project it has become clear that making this headset available to the mass market is not only feasible but necessary. Our headset could change the way depression research is conducted (through big-data crowd science) and more importantly change the faith of the more than 300 million people worldwide suffering from depression,” says Friis-Olivarius.
The team are proud to have started a crowd science movement for neurostimulation. “Crowd Science is an open research concept which consists of large-scale, user-driven experiments that we then collect the research data from,” Friis-Olivarius adds.
The consumer version, PlatoWork, is already on the market. The team expects PlatoCure to be on the market by 2022.
Reviewed by Emily Henderson, B.Sc. Dec 18 2020
A third of epilepsy sufferers are resistant to treatment for this neurological disease that affects 1% of the population. The onset of seizures is unpredictable, and has been the subject of fruitless research since the 1970s. The unforeseeable nature of the disease means patients are forced to take medication and / or adjust their lifestyles.
Neuroscientists from the University of Geneva (UNIGE) and the University Hospital of Bern (Inselspital) – working with the University of California in San Francisco (UCSF) and Brown University in Providence – have succeeded in developing a technique that can predict seizures between one and several days in advance. By recording neuronal activity over at least six months using a device implanted directly in the brain, it is possible to detect individual cycles of epileptic activity and provide information about the probability of a future seizure. This approach, published in the journal Lancet Neurology, is remarkably reliable, and prospective clinical trials are now in the pipeline.
An epileptic brain can switch suddenly from a physiological state to a pathological state, characterized by a disturbance of neuronal activity which can cause, inter alia, convulsions typical of an epileptic seizure. How and why the brain swaps one state for another is still poorly understood, with the result that the onset of a seizure is difficult, if not impossible, to predict.
Specialists worldwide have been trying for over 50 years to predict seizures a few minutes in advance, but with limited success.”
Timothée Proix, Researcher, Department of Fundamental Neurosciences, University of Geneva Faculty of Medicine
Seizures do not appear to be preceded by any obvious warning signs that would make prediction easier. The frequency, depending on the individual, varies from once a year to once a day.
“It’s a huge problem for patients”, begins Maxime Baud, a neurologist at Inselspital. “This unpredictability is associated with a permanent threat that obliges patients to take medication on a daily basis. And in many cases, it prevents them from participating in certain sports. Living with this hanging over you can also affect your mental health”. Existing treatments are often difficult to bear: they depend on drugs with numerous potential side effects to reduce neuronal excitability and sometimes involve neurosurgery to remove the epileptic focus, i.e. the starting point of the brain seizures. Moreover, a quarter of patients do not respond to these treatments, meaning they have to learn to manage the chronicity of their disease.
Epileptic activity can be measured using cerebral electrical activity data recorded by electroencephalography. This can be used to identify interictal discharges – evanescent discharges that appear in between seizures without directly causing them. “We observe clinically that epileptic seizures recur in clusters and cyclically. To ascertain whether the interictal discharges can explain these cycles and forecast the onset of a seizure, we analyzed the data in greater detail,” continues Dr Baud.
- Research shows that people affected with COVID-19 suffer from cognitive effects
- No more ICU beds at the main public hospital in the nation’s largest county as COVID surges
- Neuroscientists investigate the relationship between language and cognitive functions
To do this, Baud collaborated with Vikram Rao, neurologist at UCSF, to obtain neuronal activity data collected over several years using devices implanted long-term in the brains of patients with epilepsy. After confirming that there were indeed cycles of cerebral epileptic activity, the scientists turned their attention to statistical analysis.
This approach helped highlight a phenomenon known as the “pro-ictal state” where the probability of the onset of a seizure is high. “As with weather disturbances, there are several time scales in epileptic brain activity”, points out Dr Baud. “The weather is influenced by the cycle of the seasons or day and night. On an intermediate scale, when a weather front approaches, the probability that it will rain increases for several days and is, therefore, better predictable. These three scales of cyclic regulation also exist for epilepsy.”
The right timeframe
The electrical activity in the brain is a reflection of the cellular activity of its neurons, more precisely their action potentials, electrical signals propagating along the neural network to transmit information. Action potentials are well known to neuroscientists, and their probability can be modelled using mathematical laws. “We adapted these mathematical models to the epileptic discharges to find out whether they heralded or inhibited a seizure”, explains Dr Proix.
To boost the predictive reliability, recordings of brain activity over very long periods were required. Using this approach, fronts with a high probability of seizure lasting several days could be determined for a majority of patients, making it possible to predict seizures several days in advance in some. With brain activity data collected over periods of at least six months, seizure prediction is informative for two-thirds of patients.
The analytical approach is sufficiently “light” to allow the transmission of data in real time on a server or directly on a microprocessor with a device small enough to be implanted in the skull. The researchers are now working in collaboration with the Wyss Center for Bio and Neuroengineering, based at Campus Biotech in Geneva, to develop a minimally invasive brain monitoring device to record the long-term data needed to forecast seizures. The device, which slips under the skin of the scalp, could give people with epilepsy the power to plan their lives according to the likelihood of having a seizure.
Source: University of Geneva
Journal reference: Proix, T., et al. (2020) Forecasting seizure risk in adults with focal epilepsy: a development and validation study. Lancet Neurology. doi.org/10.1016/S1474-4422(20)30396-3.
By Rich Haridy December 20, 2020
An international study is showing, for the first time, that it may be possible to predict the onset of epileptic seizures several days in advance. By analyzing data from a clinically approved brain implant designed to monitor and prevent seizures, the new research hopes to develop a model offering patients with epilepsy a seizure forecasting tool to predict the likelihood of upcoming episodes.
The research looked at data from a responsive brain stimulation implant called NeuroPace. The device was approved for clinical uses back in 2013 and it works to prevent seizures by delivering imperceptible pulses of electrical stimulation to certain parts of the brain upon detecting abnormal brain activity.
Scientists have been working on a variety of seizure prediction tools for decades. But despite some incredible advances, such as the NeuroPace device, no innovation to date has successfully shown it possible to predict seizures more than a few minutes in advance, at best.
The NeuroPace innovation offers researchers the first chance to study the relationship between seizures and brain activity using years of EEG data. The new study initially analyzed long-term data from 18 patients with the brain implant who were closely tracked for several years. From this data the researchers developed predictive algorithms to forecast seizures. These predictive algorithms were then tested on long-term data gathered from the more than 150 people who participated in the decade-long clinical trials testing the brain implant system.
Vikram Rao, co-senior author on the new study, says the data shows seizure risk could be effectively forecasted three days ahead in nearly 40 percent of subjects and one day ahead in 66 percent of subjects.
“For forty years, efforts to predict seizures have focused on developing early warning systems, which at best could give patients warnings just a few seconds or minutes in advance of a seizure,” says Rao. “This is the first time anyone has been able to forecast seizures reliably several days in advance, which could really allow people to start planning their lives around when they’re at high or low risk.”
Rao does stress the current algorithm can only predict when one is at higher risk of seizure, and not specifically when a seizure will take place. A number of other unaccounted environmental triggers, from stress to erratic sleep, can play a role in the onset of a seizure. So the system currently developed is more like a weather forecast, offering probabilities designed to help guide a person’s future activities.
“I don’t think I’m ever going to be able to tell a patient that she is going to have a seizure at precisely 3:17 pm tomorrow—that’s like predicting when lightning will strike,” explains Rao. “But our findings in this study give me hope that I may someday be able to tell her that, based on her brain activity, she has a 90 percent chance of a seizure tomorrow, so she should consider avoiding triggers like alcohol and refrain from high-risk activities like driving.”
Much more work is needed before the system is ready for clinical use. This preliminary study uncovered a significant amount of variability from person to person. It is unclear why reliable forecasting could not be generated from some patient’s brain activity data. Future investigations to optimize the algorithm and perhaps incorporate multimodal physiological data may enhance the algorithm’s predictive capacity.
Plus, currently the system requires data gathered from a device requiring surgical implantation. This would limit the use of the device to only those with the most severe forms of epilepsy. More superficial subscalp EEG devices could offer a less invasive way of capturing this brain activity data over long periods of time.
“It is worth remembering that, currently, patients have absolutely no information about the future—which is like having no idea what the weather tomorrow might be—and we think our results could help significantly reduce that uncertainty for many people,” adds Rao. “Truly determining the utility of these forecasts, and which patients will benefit most, will require a prospective trial, which is the next step.”
The new study was published in the journal The Lancet Neurology.