tag:theconversation.com,2011:/ca-fr/topics/epilepsy-3271/articlesEpilepsy – La Conversation2024-03-28T18:54:37Ztag:theconversation.com,2011:article/2264302024-03-28T18:54:37Z2024-03-28T18:54:37ZA rare condition makes other people’s faces look distorted. Why a new case is important<p>If you’ve seen portraits painted by <a href="https://journals.sagepub.com/doi/10.1111/j.1468-2982.2000.00113.x">Pablo Picasso</a> or <a href="https://www.frontiersin.org/articles/10.3389/fnhum.2014.00581/full">Francis Bacon</a>, you might not be surprised to hear that both men may have suffered from a disorder that affects how faces are perceived. </p>
<p><a href="https://prosopometamorphopsia.faceblind.org/">Prosopometamorphopsia</a> (PMO) is a condition where faces appear distorted, and sometimes even demonic. In most cases, these distortions alter how images of faces look, as well as those seen in person. This makes it difficult for sufferers to assess the accuracy of illustrations depicting what they see because the illustration itself will appear distorted. </p>
<p>However, a case described in a <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)00136-3/abstract">recent study</a> gave researchers new insight into PMO. Unlike most other cases, the 58-year-old man (referred to as VS) perceived images of faces without distortion. Unfortunately, when he saw people in person over the last 31 months, every face appeared stretched and “demonic” to him. </p>
<p>Not to be confused with <a href="https://theconversation.com/i-should-know-you-face-blindness-and-the-problem-of-identifying-others-8884">prosopagnosia</a> (poor face recognition but without visual distortions), PMO is thought to be extremely rare and people who have it perceive faces as drooping, stretched, out of position, or either smaller or larger than normal. These distortions might apply to the whole face, <a href="https://www.sciencedirect.com/science/article/pii/S0028393208004971">only one side</a>, or even be restricted to particular features like the <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3540293/">nose and mouth</a>.</p>
<h2>What causes prosopometamorphopsia?</h2>
<p>In contrast with prosopagnosia, which can either be acquired (through injury, for example) or developmental (present from birth), PMO seems only to be the result of the former. A <a href="https://www.sciencedirect.com/science/article/pii/S0010945221000836">2021 study</a> by researchers in the Netherlands reviewed 81 cases of PMO. The causes included <a href="https://www.vinmec.com/en/news/health-news/brain-infarction-what-you-need-to-know/">brain infarction</a> (disrupted blood flow to part of the brain), <a href="https://www.ncbi.nlm.nih.gov/books/NBK559173/#:%7E:text=type%20of%20stroke.-,Hemorrhagic%20stroke%20is%20due%20to%20bleeding%20into%20the%20brain%20by,bleeding%20into%20the%20subarachnoid%20space.">haemorrhagic stroke</a> (bleeding into the brain), surgery complications, head injury, and brain tumour. However, in 24% of cases, there appeared to be no structural abnormalities to the brain. Instead, PMO was associated with other diagnoses like epilepsy, migraine and schizophrenia.</p>
<p>Reassuringly, in the majority of cases, people with PMO appear to recover from their condition. This might be either a full or partial recovery, sometimes resulting from treatments that address the underlying cause (such as anti-epileptic drugs for epilepsy, or surgery to remove a brain tumour). However, some people seem to recover without any intervention. The time for recovery ranges from hours to years, but the typical recovery period is often days to weeks. </p>
<h2>Is face recognition affected?</h2>
<p>Despite the fact that people with PMO sometimes experience seeing profound facial distortions, their ability to recognise faces rarely seems to be affected. However, sufferers may simply be relying on other cues to help with recognition, like the person’s voice or clothes. For some people, distortions only appear after seconds or minutes of seeing someone’s face, allowing them time to identify the person first. Researchers have also tried to model how PMO-like distortions could <a href="https://www.sciencedirect.com/science/article/pii/S0010945221003440">affect face recognition</a>. They found that the distance between the viewer and face played a significant role in how accurately faces were recognised by participants.</p>
<p>A <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)00136-3/abstract">recent study</a> by researchers in New Hampshire, US, focused on the case of a man known as VS. He had a lesion in his <a href="https://www.britannica.com/science/hippocampus">hippocampus</a> (a region of the brain mainly associated with memory) but no other medical issues of note.</p>
<p>Although VS saw people’s faces as stretched and with deep grooves (in his words, appearing “demonic”), facial images were unaffected for him. The researchers presented VS with in-person faces and the same faces on a computer screen. Next, the researchers used image-editing software to modify each photo so that it matched VS’s descriptions, listening to his real-time feedback. </p>
<p>It was the first time researchers could create photorealistic visualisations of these kinds of distortions, providing a depiction of how people with PMO can see those around them.</p>
<p>VS’s distortions also appeared to be <a href="https://jov.arvojournals.org/article.aspx?articleid=2792559">affected by colour</a>, so researchers investigated what happened when VS viewed faces through coloured plastic filters. They found that green filters decreased, and red filters intensified, the distortions compared with the no-filter baseline. These results showed that colour filters worn in glasses could reduce face distortions in PMO, and that colour might affect how we perceive face shape in general.</p>
<h2>What can we learn?</h2>
<p>As researchers continue to build on our knowledge of PMO, it is likely that more insights will be revealed about how the general population processes faces. Among the <a href="https://www.sciencedirect.com/science/article/pii/S0028393223000519">many questions</a> yet to be answered, some involve how and where faces are represented in the human brain. We also still have a lot to learn about the specific nature of PMO’s distortions, what they can tell us, and why they seem to resolve themselves in some cases but not others. For now, PMO is both a fascinating and disturbing condition, and one that could potentially teach us a great deal about human face perception.</p>
<p>Given that PMO is so rare and we still have so much to learn about it, please consider getting in touch with me (the <a href="https://staff.lincoln.ac.uk/rkramer">author</a> of this article) if you think you may be suffering from it. Remember that those with PMO don’t really think that the world is distorted, and instead realise that their vision is different in some way.</p><img src="https://counter.theconversation.com/content/226430/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Robin Kramer does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>A highly unusual new case is giving scientists insights about what causes illusions of facial distortionRobin Kramer, Senior Lecturer in the School of Psychology, University of LincolnLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2207482024-02-14T13:21:02Z2024-02-14T13:21:02ZRecognizing when someone is having a seizure – and how you can help during those first critical moments<figure><img src="https://images.theconversation.com/files/574237/original/file-20240207-24-u7tbcw.jpg?ixlib=rb-1.1.0&rect=0%2C45%2C7680%2C4265&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Seizures occur because of sudden and abnormal activity in the brain.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/neuron-system-disease-royalty-free-image/1434534146?phrase=epilepsy&adppopup=true">koto_feja/E! via Getty Images</a></span></figcaption></figure><p><em>Approximately 1 in 26 people develop <a href="https://www.who.int/news-room/fact-sheets/detail/epilepsy#">epilepsy</a>, a condition in which someone experiences recurring and unprovoked seizures. But <a href="https://theconversation.com/silent-subtle-and-unseen-how-seizures-happen-and-why-theyre-hard-to-diagnose-184740">experiencing a seizure</a> does not always mean a person has epilepsy. Seizures can be provoked by acute head injuries, alcohol withdrawal and <a href="https://my.clevelandclinic.org/health/diseases/9815-hyperglycemia-high-blood-sugar">high blood sugar</a>, among other things. Approximately 1 in 10 people will <a href="https://www.cdc.gov/epilepsy/about/first-aid.htm#">experience a seizure during their lifetime</a>.</em> </p>
<p><em>The Conversation asked <a href="https://som.cuanschutz.edu/Profiles/Faculty/iframeProfile/30305">Dr. Jacob Pellinen</a>, a neurologist <a href="https://scholar.google.com/citations?user=DMld-5MAAAAJ&hl=en">specializing in epilepsy</a>, to walk us through how to recognize a seizure in a bystander or loved one, and what to do in those crucial moments after a seizure begins.</em></p>
<h2>What does a seizure look like?</h2>
<p>It varies. For some people, their seizure is a purely internal sensation. To an untrained observer, it may appear as though nothing’s wrong. In fact, most people with epilepsy have only relatively subtle, nonconvulsive seizures at first, then <a href="https://doi.org/10.1111/epi.16707">develop convulsive seizures over time</a>. </p>
<p>But others having seizures experience full body convulsions with a loss of consciousness. This is the type of seizure most of us are familiar with, probably because it’s the kind most frequently depicted, though not always accurately, in movies and on television. It’s also <a href="https://www.mountsinai.org/health-library/diseases-conditions/generalized-tonic-clonic-seizure#">the most dangerous type of seizure</a>.</p>
<p>These kinds of seizures are sudden, unprovoked and last a couple of minutes. After recovering from the convulsions and loss of consciousness, the person is usually fatigued and confused <a href="https://doi.org/10.1016/j.yebeh.2021.108484">for several minutes to several hours</a>. </p>
<p><a href="https://www.epilepsy.com/what-is-epilepsy">If someone has epilepsy</a>, the seizures they experience will be <a href="https://doi.org/10.1111/epi.12550">very similar each time they occur</a>. The most common type of epileptic seizure are those that are focal – that is, they arise from a confined region of the brain. This accounts for two-thirds of cases overall and <a href="https://doi.org/10.1111/j.1528-1167.2009.02481.x">99% of cases that occur after the age of 25</a>. </p>
<p>Epileptic seizures may begin with nonconvulsive symptoms, including staring, unresponsiveness, repetitive movements and purely internal sensations, which either stop or progress to convulsions and loss of consciousness. </p>
<h2>What causes a seizure to occur?</h2>
<p>Seizures are the result of <a href="https://epilepsydiagnosis.org/seizure/seizure-classification-groupoverview.html">abnormal electrical activity in the brain</a>. The bursts of activity disrupt normal functioning and initiate hyperactivity in the affected brain area, which then can affect the corresponding body part. </p>
<p>For instance, if the seizure arises from the part of the brain involved in arm movement, that arm will experience involuntary hyperactivity.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/572338/original/file-20240131-21-c72v6r.jpg?ixlib=rb-1.1.0&rect=0%2C7%2C5120%2C3395&q=45&auto=format&w=1000&fit=clip"><img alt="An illustration of chaotic brain waves during a seizure event." src="https://images.theconversation.com/files/572338/original/file-20240131-21-c72v6r.jpg?ixlib=rb-1.1.0&rect=0%2C7%2C5120%2C3395&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/572338/original/file-20240131-21-c72v6r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/572338/original/file-20240131-21-c72v6r.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/572338/original/file-20240131-21-c72v6r.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/572338/original/file-20240131-21-c72v6r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/572338/original/file-20240131-21-c72v6r.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/572338/original/file-20240131-21-c72v6r.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Lengthy or back-to-back seizures can be life-threatening.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/brain-and-brain-waves-in-epilepsy-royalty-free-illustration/973895676?phrase=seizure&adppopup=true">Kateryna Kon/Science Photo Library via Getty Images</a></span>
</figcaption>
</figure>
<h2>If you’re a bystander, how can you help?</h2>
<p>First, <a href="https://www.epilepsy.com/recognition">keep the person safe</a>. Many seizure-related injuries occur due to falling or coming in contact with sharp or hard objects. If they begin to fall, help them to the floor as gently as possible and put something soft under their head.</p>
<p>During the convulsive phase of a seizure, breathing may be intermittent. So turn the person on their side so they can breathe more easily and lower the risk of aspiration. </p>
<p>Do not put any objects into their mouth. This is unnecessary and dangerous. It is <a href="https://doi.org/10.1016/j.seizure.2020.09.023">not possible to swallow your tongue</a>.</p>
<p>Do not restrain or shout at them. Neither one of those things will stop the seizure. </p>
<p>Although not everyone with epilepsy has one, check for any visible medical identification such as a wristband.</p>
<p>If they stop convulsing, but remain unresponsive, continue to keep them on their side and monitor their breathing.</p>
<p>Following the seizure, and as the person gradually recovers and wakes up, help them sit up in a safe space. If they are confused, reorient them and don’t let them wander near roads, stairs or platforms. </p>
<p>Do not give them water or food until they are fully awake. Stay with them until they are fully alert. It’s also important to tell them what happened, and offer to help further. </p>
<p>Keeping track of time is critical. Call 911 if the seizures last more than five minutes or if they begin to cluster back to back, such as when another seizure begins before a person fully recovers from the first. Although rare, <a href="https://www.hopkinsmedicine.org/health/conditions-and-diseases/status-epilepticus#">both of these situations are life-threatening emergencies</a>.</p>
<p>You should also call 911 if the person continues to have difficulty breathing; if the person has a seizure in water or is pregnant; if it’s the first time they’ve had a seizure; or if they have the seizure without a diagnosis of epilepsy. </p>
<p>However, if a person diagnosed with epilepsy experiences a habitual seizure, recovers fully and does not experience any injury, they may not need to go to the emergency room for further evaluation. They should, however, call their doctor.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/RodeQ86_bxY?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Although seeing a person having a seizure is a scary experience, there are many things you can do to help.</span></figcaption>
</figure>
<h2>Are new treatments available?</h2>
<p>People with epilepsy, particularly those who experience frequent seizures, will often have emergency medications in their possession. </p>
<p>The most common emergency medications – <a href="https://www.epilepsy.com/recognition/rescue-medications">also called seizure rescue medications</a> – are a type of anticonvulsants called benzodiazepines. The most common ones used are diazepam, clonazepam, lorazepam and midazolam. </p>
<p>All are fast-acting medications. Some are pills to be swallowed, others are dissolvable tablets placed in the cheek or under the tongue, and some are nasal sprays or gels for rectal administration. Patients and their caretakers may have access to rescue medications and know how to use them. </p>
<p>One cautionary note: If the medication is in pill form, and if the person is in the midst of a convulsive seizure, don’t put the pill in their mouth. But remember: Not all seizures are convulsive or cause a loss of consciousness. So if a person is awake and alert, they may be able to swallow a pill. </p>
<h2>What if it’s not a seizure?</h2>
<p>If a bystander does not witness a seizure, but instead finds someone unresponsive or minimally responsive, call 911. They may be suffering from other medical issues, such as a drug overdose. </p>
<p>And if you are interested in training and certification for seizure first aid, or if you simply want to know more, the Epilepsy Foundation <a href="https://www.epilepsy.com">has more information</a>.</p><img src="https://counter.theconversation.com/content/220748/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jacob Pellinen has received research support from the Department of Neurology at the University of Colorado School of Medicine, the Colorado Clinical and Translational Sciences Institute, NIH/NINDS, and the American Epilepsy Society. J. Pellinen serves as chair of the professional advisory board for the Epilepsy Foundation of Colorado and Wyoming (unpaid), serves as the Epilepsy Section Editor for Current Neurology and Neuroscience Reports, and has received compensation for serving on the scientific advisory board for SK Life Science.</span></em></p>What you don’t do: Don’t shout at them, don’t put things in their mouth and don’t let them get near things that are sharp or hard in case of a fall.Jacob Pellinen, Assistant Professor of Neurology, University of Colorado Anschutz Medical CampusLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2169622023-11-03T17:29:55Z2023-11-03T17:29:55ZBrooke Shields had a grand mal seizure – here’s what you need to know about the condition<figure><img src="https://images.theconversation.com/files/557459/original/file-20231103-21-94pua8.jpg?ixlib=rb-1.1.0&rect=4%2C4%2C2991%2C1989&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Shields suffered the seizure in September 2023.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/los-angeles-jun-8-brooke-shields-104740769">Joe Seer/ Shutterstock</a></span></figcaption></figure><p>Actress and model Brooke Shields has revealed she suffered a <a href="https://www.glamour.com/story/brooke-shields-glamour-women-of-the-year-2023">grand mal seizure</a> in September. In an interview, Shields revealed that the seizure caused her to lose control of her movements, froth at the mouth and eventually lose consciousness. The actress doesn’t have a history of seizures – and many people reading her story may be wondering if they’re also at risk.</p>
<p>“Grand mal”, which means “great sickness” in French, is actually the old term for what’s now called a <a href="https://www.cdc.gov/epilepsy/about/types-of-seizures.htm">tonic-clonic seizure</a>. These seizures involve both stiffening (tonic) and twitching (clonic) muscle movements. It’s just one type of seizure a person can experience. </p>
<p>Seizures happen when the electrical activity in our brain becomes disrupted.</p>
<p>Normally, the electrical activity in our brains carries information inward from the sensory world around us, outward to our muscles, and also transmits our thoughts, feelings and intentions everywhere else in between. To carry all this information, the brain activity forms complex patterns – like how the pixels on your computer or phone’s screen form complex patterns of colour and shape to bring you the information you’re reading now.</p>
<p>But <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4448698/">during a seizure</a>, the electrical activity in some or all of the brain instead enters a rhythmic sequence, alternating between high and low-intensity activity. This disrupts the information being sent and received in those parts of the brain. Think of it like your computer or phone screen suddenly being covered only in alternating black and white stripes. This on/off pattern is an extreme type of neural oscillation.</p>
<p>The symptoms a person experiences during a seizure depends on the brain region being affected.</p>
<p>Tonic-clonic seizures, which involve muscle stiffening and twitching, usually involve large parts of the cerebral cortex – the outer, wrinkly layers of the brain. Because of this, they are referred to as generalised seizures and they affect the motor cortex, which controls the body’s voluntary muscle movements. This brain area would have been involved in Shields’ seizure.</p>
<p>Other types of seizures include absence seizures (formerly known as petit mal, or “little sickness”) and focal seizures. </p>
<p>Absence seizures also involve large parts of the cerebral cortex. These cause a person to suddenly stop all activity and stare ahead of them with a blank look. Their eyes may also turn upwards. Researchers aren’t quite sure why absence seizures and tonic-clonic seizures have such different symptoms, but it might be down to the <a href="https://pubmed.ncbi.nlm.nih.gov/36627270/">patterns of activity</a> that make up the seizures. </p>
<p>Focal seizures, on the other hand, happen only in part of the cerebral cortex. Symptoms will depend on the function of the brain area affected by the seizure. If it’s a motor region, some muscle twitches might be observed. </p>
<p>The affected brain regions usually go back to working as normal after the seizure ends – either straight away or after some minutes. In unusual cases, the <a href="https://www.ncbi.nlm.nih.gov/books/NBK526004/#:%7E:text=Continuing%20Education%20Activity,%2C%20headache%2C%20nausea%2C%20etc.">post-seizure state</a> can last for hours. </p>
<p>If a person has a seizure more than once, they might be <a href="https://www.nhs.uk/conditions/epilepsy/">diagnosed with epilepsy</a> – a lifelong condition that causes frequent seizures. But some people – like Shields – can have a one-off seizure caused by temporary changes in their environment or body.</p>
<h2>Disrupted brain patterns</h2>
<p>Anything that sufficiently disrupts our <a href="https://pubmed.ncbi.nlm.nih.gov/21861061">brain’s normal patterns</a> of activity has the potential to cause seizures.</p>
<p>While such disruptions usually only happen as part of an epilepsy syndrome, they can also happen when the body (and therefore the brain) is put under <a href="https://www.mayoclinic.org/diseases-conditions/grand-mal-seizure/symptoms-causes/syc-20363458">extreme stress</a>. Potential causes of this stress include a stroke, brain trauma, a fever and very low blood sugar.</p>
<p>Shields has said that her tonic-clonic seizure was caused by drinking too much water, resulting in low blood sodium levels. This condition, known as <a href="https://www.mayoclinic.org/diseases-conditions/hyponatremia/symptoms-causes/syc-20373711">hyponatraemia</a>, has significant consequences for the brain – most notably a swelling of brain cells as their water content increases. </p>
<p>Because the brain is contained within the skull it doesn’t have room to freely expand. As such, it has mechanisms in place to counteract increases in water content. Some of these mechanisms can throw off the delicate balance of the charged particles (ions) that allow the brain to be electrically active. </p>
<p>This could in turn alter the electrical activity in the brain and lead to the seizures that are sometimes observed in <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4470176/">advanced cases of hyponatraemia</a>.</p>
<p>While hyponatraemia is a very rare cause of tonic-clonic seizures, it’s still worth being aware that it can sometimes cause them. This may particularly be a concern to older people and those staying in hospital long-term, as certain treatments and medications (such as diuretics) can disrupt sodium levels. </p>
<p>For most of us, this is not a significant risk. Our bodies normally tell us when we’ve had enough water, and we typically consume enough salt in our diet to maintain balance. </p>
<p>And, because our brains typically only become vulnerable to one-off seizures in extreme conditions – such as a very unusual diet, alcohol or drug overuse, extreme exhaustion, or trauma – they aren’t something the majority of us will need to worry about.</p><img src="https://counter.theconversation.com/content/216962/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Cian McCafferty has been a member of, and received funding from, the Epilepsy Foundation.</span></em></p>Shields said the seizure was caused by drinking too much water – which can be a cause in very rare circumstances.Cian McCafferty, Lecturer and Researcher, Department of Anatomy & Neuroscience, University College CorkLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2110842023-08-25T13:39:37Z2023-08-25T13:39:37ZSetting the stage for a better understanding of complex brain disorders<p>We often compare the brain to a machine with wheels, cogs, and belts. In this analogy, when something breaks, the entire mechanism skips a beat or grinds to a halt. However, more often than not this isn’t what happens with our brains. Instead, they’re more like a theatre. Here, neurons are the musicians, actors, and dancers, and they improvise a performance that shapes our thoughts and lives.</p>
<p>I’m an electronic and computer engineer at the <a href="https://www.epu.ntua.gr/">DSS Lab</a> of the National Technical University of Athens. In December 2019, Ioannis Stavropoulos, a neuroscientist at King’s College London, introduced me to his colleague Elissaios Karageorgiou of the Neurological Institute of Athens. They wanted to talk about an idea they had about neurology and, in a way, theatre, over coffee.</p>
<p>In any piece of theatre, mistakes happen – a violin might miss a note, a drummer could skip a beat, an actor might muddle a line or a dancer stumble. Sometimes, many things go wrong simultaneously, and the audience is left wondering what’s going on. Was it the singer who was off? Was it the pianist who hit the wrong chord? Did the lights go off at the wrong time and confuse them both?</p>
<p>Complex brain disorders (CoBraD) are very much like that. These include Alzheimer’s disease, sleep problems, and epilepsy. We see their symptoms as performance missteps, yet it’s hard to group, label, and know their causes. When multiple symptoms show up at once, diagnosis becomes particularly challenging.</p>
<p>It would be hard to know what’s wrong in a musical or play by just listening to a second or two every half hour. Similarly, it’s tougher to diagnose a medical problem if we only check the patient briefly, such as during occasional doctor visits. As a result, CoBraDs may stay under- or undiagnosed for a long time or be misdiagnosed. More than one can exist at the same time, and the diagnosis and treatment are expensive, at times inaccessible for patients, and often ineffective.</p>
<h2>Paying attention to the whole performance</h2>
<p>Much like how a piece of theatre relies on each artist to play her or his part well for a captivating performance, diagnosing CoBraDs demands a wide range of accurate and harmonised data. Alzheimer’s, sleep disorders, and epilepsy are among the conditions that Ioannis and Elissaios are studying and treating. Recognising the limitations of traditional diagnostic methods, they turned their attention to real-world data (RWD), meaning data collected directly from patients not taking part in a clinical trial.</p>
<p>Data gathered from <a href="https://www.who.int/health-topics/clinical-trials">clinical trials</a> are more reliable than real-world data – they’re the result of experiments performed in strict and controlled conditions. However, they are often hard and expensive to get, limited in size, and they may not fully represent the complexity and variability of the real world.</p>
<p>In contrast, real-world data encompass a wider array of information sources, from electronic health records and patient visits to medical devices like MRIs and wearables. When aggregated, these diverse data points become “big data”, offering a more comprehensive view of patient health. This holistic approach can reveal patterns and insights that might be missed in more conventional, narrower diagnostic methods.</p>
<p>Collecting significant amounts of real-world data is just the beginning. The real challenge lies in harmonising and analysing it all to extract meaningful insights and then finding ways to use them to diagnose and treat patients. To achieve this, we sought expertise from various scientific disciplines. What became our vision was to create a digital platform where neuroscientists could store and share large amounts of data, analyse them, and use them to devise new diagnostic processes and criteria that would be more complex and nuanced than what human clinicians can handle.</p>
<p>These processes would be built into the platform to support clinicians in making decisions for their patients when diagnosing or treating them. These are called decision support systems, and when they use tools like artificial intelligence, enhancing the competences of human experts in a technical or scientific field, they’re called expert systems.</p>
<p>Scientists have proposed numerous ideas hinting that faint clues and varied signals might point to early detection of CoBraD. Many remain unproven, and some are tough to track without computers. For instance, slight changes in sleep, coupled with specific MRI signs, could suggest an early brain disorder. Rather than waiting years for clear symptoms to emerge, doctors could act swiftly, improving the patient’s prospects.</p>
<p>This is how the idea for the <a href="https://www.mes-cobrad.eu/">Multidisciplinary Expert System for the Assessment and Management of Complex Brain Disorders</a> (MES-CoBraD) was born. Bringing together with experts in medicine, engineering, and computer science, we are building a software platform and performing medical research using it.</p>
<h2>When doctors, practitioners, software engineers and AI work together</h2>
<p>MES-CoBraD evolved into an EU-funded project that now includes 14 universities, companies, and hospitals across Europe. The underlying concept is straightforward: data and observations produced by clinical practice are used by medical research to enhance that very practice.</p>
<p>This continuous circular collaboration can use technology as a link and an enabler. Researchers and clinicians collect and anonymise patient data and upload them to the platform. The researchers form scientific hypotheses, analyse the data, train AI models, and test their hypotheses.</p>
<p>Should they achieve a breakthrough, clinicians would be able to directly use the platform’s algorithms to diagnose patients and provide treatments. Related data would in turn will be anonymised and serve to test new hypotheses, aid new statistical analyses, train AI models, or refine existing ones.</p>
<p>The challenges are many. When designing new experiments, we must ensure our data are unbiased. We are also investigating and addressing the ethical implications of using artificial intelligence in medicine. For instance, how do we guarantee that its suggestions are understood by the clinician and can be explained to the patient? How can we be certain that they don’t inadvertently favour one patient group over another, or prioritise cost savings over human life? If AI makes a mistake, who takes responsibility?</p>
<p>In MES-CoBraD, we have been venturing into some uncharted territory, but always with specific goals in mind. Although the platform is being made to work in multiple medical fields, the focus now is finding ways of using a very detailed picture of patients’ health (a process called deep phenotyping) in conjunction with advanced analytics tools and AI to diagnose and manage CoBraDs. In essence, we aim to simultaneously tune the instruments, hone the actors’ lines, and adjust the score.</p>
<h2>A personal turn on the stage</h2>
<p>Interestingly, my own life’s “play” has its moments of dissonance, as I sometimes wake in the middle of the night and find it hard to get back to sleep. I don’t think it’s anything serious, but as a scientist and longtime researcher, I would never miss the chance to test our own methods and processes on myself. I thus signed up as a test subject for our sleep study and wore a device called <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/actigraphy">“actigraph”</a> on my wrist for a week, and it kept track of my activities, diet, and sleep. I took memory tests and answered questions, and finally there was the main event: I got hooked up with around 40 or 50 cables, tubes and sensors, and slept in the clinic for the night. As a bonus, I offered months of smartwatch health data, which was anonymised and included in the platform.</p>
<p>I am happy to report that for now my sleep issues are likely to be stress-related. However, if deep phenotyping and AI end up diagnosing something worse – say, an early onset complex brain disorder – the question for someone in my position would be: “Should I worry or celebrate the scientific breakthrough if it does?”</p>
<hr>
<p><em>This article is the result of The Conversation’s collaboration with <a href="https://ec.europa.eu/research-and-innovation/en/horizon-magazine">Horizon</a>, the EU research and innovation magazine. In June the magazine published an <a href="https://ec.europa.eu/research-and-innovation/en/horizon-magazine/brain-disorders-trigger-search-new-clues-and-cures">interview with the authors about their research</a>.</em></p><img src="https://counter.theconversation.com/content/211084/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Christos Ntanos is the Project Coordinator of the "MES-CoBraD -- Multidisciplinary Expert System for the Assessment & Management of Complex Brain Disorders" project, which has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 965422.</span></em></p>Disorders such as Alzheimer’s and epilepsy are difficult to diagnose with only occasional doctor visits. A new approach would allow fathering of extensive real-world data directly from patients.Christos Ntanos, Research director at the Decision Support Systems (DSS) Laboratory, National Technical University of AthensLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2082812023-08-17T01:00:49Z2023-08-17T01:00:49ZWhat is sudden unexpected death in epilepsy, and what causes it?<figure><img src="https://images.theconversation.com/files/541171/original/file-20230804-17-ze86rg.jpg?ixlib=rb-1.1.0&rect=20%2C20%2C6689%2C4446&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>When 20-year-old Disney Channel star Cameron Boyce died of “sudden unexpected death in epilepsy” (known as <a href="https://www.epilepsy.com/complications-risks/early-death-sudep">SUDEP</a>) in 2019, his parents had not even heard of the condition.</p>
<p>“We didn’t know about SUDEP. We have family members who are doctors who never heard of SUDEP,” Cameron’s father Victor said in an <a href="https://www.healthline.com/health/epilepsy/cameron-boyce-foundation-interview">interview</a>. </p>
<blockquote>
<p>We were clueless, completely clueless. The first time we heard [of] SUDEP is when the coroner told us that’s what took our son.</p>
</blockquote>
<p>Most of us have heard of <a href="https://www.epilepsy.com/what-is-epilepsy">epilepsy</a>, a brain condition that causes recurrent and spontaneous seizures. Lesser known to the public is that seizures can lead to an uncommon but fatal complication known as sudden unexpected death in epilepsy.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1686840516090937344"}"></div></p>
<h2>What is sudden unexpected death in epilepsy?</h2>
<p>Sudden unexpected death in epilepsy is when someone with epilepsy dies without any warning and there is no other cause found. It often occurs immediately after a night-time convulsive seizure. Victims are often found in bed and lying face down. </p>
<p>While this can occur at any age, it particularly affects young people – the average age at death is only <a href="https://n.neurology.org/content/93/3/e227">26 years</a>.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1686626715013963776"}"></div></p>
<p>The risk of sudden unexpected death in epilepsy is highest in those who have <a href="https://www.epilepsy.com/what-is-epilepsy/seizure-types/tonic-clonic-seizures">convulsive or “tonic-clonic” seizures</a>. With these types of seizures, the muscles stiffen, there is loss of consciousness, and the body starts jerking rhythmically. </p>
<p>This can cause a fast heart rate, as well as long pauses to breathing, which decrease oxygen levels. These seizures can place a lot of stress on the body.</p>
<p>Even one convulsive seizure in the past year can increase the risk of sudden unexpected death in epilepsy. In one Swedish study, having one convulsive seizure and not sharing a bedroom (meaning no-one is there to intervene if a seizure occurs in the night) made the condition <a href="https://n.neurology.org/content/94/4/e419">67 times more likely</a> than those who do not have convulsive seizures and share a bedroom. As the number of convulsive seizures increase, the risk of sudden unexpected death also increases.</p>
<p>Sudden unexpected death in epilepsy is the leading cause of death from epilepsy and accounts for over <a href="https://n.neurology.org/content/98/3/e213">80% of epilepsy deaths</a>. </p>
<p>While the overall risk of SUDEP is low, with about 1 in 1,000 people with epilepsy affected each year, this risk increases to 1 in 150 in those with poorly controlled <a href="https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(08)70202-3/fulltext">seizures</a>. The <a href="https://www.nejm.org/doi/full/10.1056/nejmoa0911610">risk</a> increases with time, as epilepsy is often a lifelong condition, and the longer the exposure, the higher the risk. </p>
<p>But these figures are thought to be an underestimate. Because deaths commonly occur at night, they aren’t often witnessed, limiting what information there is about the time of death – for instance, whether there a seizure right before death. Often, victims are found deceased in bed and a history of epilepsy is overlooked as the cause of death.</p>
<p>People with epilepsy often have other serious medical problems such as <a href="https://www.ahajournals.org/doi/10.1161/JAHA.121.021170">heart disease</a>, which can make identifying the cause of death difficult. </p>
<p>Autopsy findings are often inconclusive or <a href="https://n.neurology.org/content/89/9/878">attributed to heart issues</a>, as even among forensic specialists there is <a href="https://n.neurology.org/content/89/9/886">limited awareness</a> that epilepsy can cause sudden death.</p>
<h2>Do we know what causes sudden unexpected death in epilepsy?</h2>
<p>It’s still unclear why one person can have hundreds of convulsive seizures in their lifetime and won’t die of sudden unexpected death in epilepsy, and yet another can die after only a handful. </p>
<p>We think this is because there are <a href="https://www.epilepsy.com/complications-risks/early-death-sudep/how-sudep-occurs">many different causes</a>. </p>
<p>Looking at sudden unexpected death in epilepsy cases <a href="https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(13)70214-X/fulltext">that happened in hospital</a>, researchers found that in all cases, a convulsive seizure caused a “flat-lining” of brain activity, which stopped the heart beat and breathing – all within minutes, causing rapid death. Survivors in this study all received prompt resuscitation within minutes.</p>
<p>But in some people, seizures can trigger dangerous irregular heart <a href="https://n.neurology.org/content/98/19/e1923.long">rhythms</a> – which may be <a href="https://cp.neurology.org/content/11/5/e747">another cause</a> of the sudden death.</p>
<p>Some genetic conditions can impair how molecules responsible for electrical conduction in the heart and brain function. This can increase the risk of sudden unexpected death in epilepsy by making <a href="https://onlinelibrary.wiley.com/doi/10.1002/ana.24596">epilepsy and abnormal heart conditions</a> more likely to occur together, heightening the risk of death.</p>
<p>Seizures can deprive the major organs of oxygen. Over time, repeated decreases in oxygen levels can cause damage to not only the heart, but also to the brain. </p>
<p>In people who died of sudden unexpected death in epilepsy, areas of the brain that control breathing and heart function had <a href="https://onlinelibrary.wiley.com/doi/10.1111/epi.14689">shrunk</a>. Over time, this may increase the risk of sudden unexpected death in epilepsy by lowering the brain’s ability to control vital functions.</p>
<h2>I or a loved one have epilepsy. What can we do?</h2>
<p>Unfortunately, people with epilepsy and their families are often not <a href="https://www.ilae.org/files/ilaeGuideline/AES_SUDEP_Position_Statement_2019.pdf">counselled</a> on sudden unexpected death in epilepsy and its risks. All newly diagnosed epilepsy patients should be informed about these risks at the time of diagnosis or shortly afterwards.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1686708929789665281"}"></div></p>
<p>Individual risk varies. For most people with epilepsy, the overall risk will be low. Control of convulsive seizures is associated with the most significant risk reduction. </p>
<p>Most of the time this is achieved with the use of one or more <a href="https://www.epilepsy.com/stories/summary-anti-seizure-medications">epilepsy medications</a>. </p>
<p>In people who don’t respond to epilepsy medications, <a href="https://www.mayoclinic.org/tests-procedures/epilepsy-surgery/about/pac-20393981">brain surgery</a>, <a href="https://onlinelibrary.wiley.com/doi/abs/10.1111/epi.17329#pane-pcw-references">implantable neurostimulators</a>, or <a href="https://www.epilepsy.com/treatment/dietary-therapies/ketogenic-diet">dietary therapies</a> may offer some people hope in decreasing seizure frequency.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/what-are-ketogenic-diets-can-they-treat-epilepsy-and-brain-cancer-83401">What are ketogenic diets? Can they treat epilepsy and brain cancer?</a>
</strong>
</em>
</p>
<hr>
<p>It’s important to remember sudden unexpected death in epilepsy can happen to anyone with epilepsy – even those with well-controlled epilepsy. </p>
<p>Taking medications as prescribed and not missing doses, getting a good night’s sleep, avoiding alcohol and recreational drugs, and managing stress may reduce the risk of sudden unexpected death in epilepsy by making <a href="https://www.epilepsy.com/what-is-epilepsy/seizure-triggers">seizures less likely</a>. </p>
<p>For some people who continue to have convulsive seizures, <a href="https://n.neurology.org/content/94/4/e419">sharing a bedroom</a>, or <a href="https://epilepsyfoundation.org.au/understanding-epilepsy/epilepsy-and-seizure-management-tools/seizure-monitors-devices/">night-time monitoring devices</a> may offer peace of mind and help with sudden unexpected death in epilepsy risk.</p>
<p>The causes of sudden unexpected death in epilepsy are many – understanding these will help develop targeted treatments. We need to develop tests that can identify people at high risk so we can optimise prevention strategies. </p>
<p>The development of night-time monitoring systems to identify dangerous seizures in the home and alert caregivers or emergency services is currently underway, and are sorely needed.</p><img src="https://counter.theconversation.com/content/208281/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Shobi Sivathamboo receives funding from the National Institutes of Health. She is affiliated with The International League Against Epilepsy SUDEP Task Force.</span></em></p>Most of us have heard of epilepsy. Lesser known to the public is that seizures can lead to an uncommon but fatal complication known as sudden unexpected death in epilepsy.Shobi Sivathamboo, Research Fellow, Monash UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/2069142023-07-11T12:30:49Z2023-07-11T12:30:49ZImmune cells in the brain may reduce damage during seizures and promote recovery, according to study in mice<figure><img src="https://images.theconversation.com/files/536347/original/file-20230707-29-x9vfl9.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1977%2C1514&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Microglia perform many functions in the brain, and their role in seizures is unclear.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/nerve-cell-conceptual-illustration-royalty-free-illustration/1359390614">KTSDesign/Science Photo Library via Getty Images</a></span></figcaption></figure><p>Seizures are like sudden electrical storms in the brain. Seizure disorders like epilepsy affect <a href="https://www.cureepilepsy.org/for-patients/understanding/basics/what-is-epilepsy/">over 65 million people worldwide</a> and can have profound effects on a person’s quality of life, cognitive function and overall well-being. Prolonged seizures called <a href="https://www.epilepsy.com/complications-risks/emergencies/status-epilepticus">status epilepticus</a> can cause lasting brain damage.</p>
<p>Specialized immune cells in the brain <a href="https://theconversation.com/harnessing-the-brains-immune-cells-to-stave-off-alzheimers-and-other-neurodegenerative-diseases-193606">called microglia</a> are activated during seizures to help clean up the damage. Researchers don’t fully understand exactly how these cells are involved in seizures. Some studies have found that microglia <a href="https://doi.org/10.1002%2Fbrb3.403">promote seizures</a>, while other studies <a href="https://doi.org/10.1016/j.bbi.2020.06.028">show the opposite</a>.</p>
<p>I am a scientist who studies the roles that microglia play in seizures. My colleagues and I at the <a href="https://www.microgleyolab.com">Eyo Lab</a> at the University of Virginia wanted to investigate the possible protective function microglia serve during seizures and how they affect recovery.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/LcO9YU-Pdws?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">The exact neurobiology of seizures remains unclear.</span></figcaption>
</figure>
<p>We induced seizures in mice using three different methods – chemical, hyperthermic and electrical – and temporarily removed their microglia. In all three cases, we found that <a href="https://doi.org/10.1002/glia.24364">seizures worsened</a> when these cells were absent. Mice without microglia also experienced significant weight loss and decrease in mobility compared with mice with microglia. </p>
<p>Our findings highlight the importance of microglia in safeguarding the brain during seizures and promoting recovery; but they also raise important questions about how these cells provide a protective rather than detrimental effect.</p>
<p>While removing all microglia allowed us to better understand their overall effects on seizures, it meant we were unable to fully assess their contributions in specific brain regions and how they interact with other cells. This is because removing microglia also affects the function of other brain cells. Future studies that more selectively modify microglia or alter their function in a controlled way could help researchers gain a more nuanced understanding of the role these cells play in seizures.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/JmQIaOp4vKs?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">This video shows microglia moving in cell culture.</span></figcaption>
</figure>
<p>Researchers also don’t fully understand what specific molecules and signals microglia use to protect the brain during seizures. How well our findings apply to seizure disorders like epilepsy is also unclear. These knowledge gaps highlight the complexity of seizure disorders and the need for continued study.</p>
<p>Identifying strategies to harness the beneficial functions of microglia can help researchers develop better treatments that prevent long-term brain damage and enhance the quality of life of people with seizure disorders.</p><img src="https://counter.theconversation.com/content/206914/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Synphane Gibbs-Shelton receives funding from the National Institutes of Health.</span></em></p>Seizures are like sudden electrical storms in the brain that can cause lasting damage. A set of immune cells in the brain called microglia may provide protection.Synphane Gibbs-Shelton, Ph.D. Candidate in Pharmacology, University of VirginiaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1950152022-11-21T11:36:24Z2022-11-21T11:36:24ZGroundbreaking studies of Earth’s churning oceans recognised at Australia’s most prestigious science prizes this year<figure><img src="https://images.theconversation.com/files/496396/original/file-20221121-14-7m0lqx.jpg?ixlib=rb-1.1.0&rect=609%2C0%2C6173%2C4311&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://svs.gsfc.nasa.gov/cgi-bin/details.cgi?aid=3827">Greg Shirah/NASA Scientific Visualisation Studio</a></span></figcaption></figure><p>This year, Australia’s prestigious Prime Minister’s Prize for Science has been awarded to a physical oceanographer whose work has had a “transformative impact” on our understanding of Earth’s oceans.</p>
<p>Professor Trevor McDougall AC from the University of New South Wales has made major contributions to unveiling the fundamental physics of the ocean.</p>
<p>During his illustrious career, McDougall has discovered previously unknown ocean mixing processes – the turbulent ways seawater churns and <a href="https://www.uib.no/en/rg/fysos/53334/ocean-mixing">irreversibly changes</a> under various conditions.</p>
<p>His discoveries have improved climate models, allowing us to better predict our planet’s fast-changing future.</p>
<p>“The ocean is notoriously difficult to observe; we know more about the surface of the Moon than we do about the seafloor,” McDougall said.</p>
<p>“We study the ocean because it transports a lot of heat from the equatorial regions towards the poles and also because it acts as the thermal flywheel of the climate system.” </p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/496389/original/file-20221121-12-1clq6g.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="A smiling older gentleman looking at the camera with the sea in the background" src="https://images.theconversation.com/files/496389/original/file-20221121-12-1clq6g.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/496389/original/file-20221121-12-1clq6g.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=900&fit=crop&dpr=1 600w, https://images.theconversation.com/files/496389/original/file-20221121-12-1clq6g.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=900&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/496389/original/file-20221121-12-1clq6g.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=900&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/496389/original/file-20221121-12-1clq6g.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1131&fit=crop&dpr=1 754w, https://images.theconversation.com/files/496389/original/file-20221121-12-1clq6g.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1131&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/496389/original/file-20221121-12-1clq6g.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1131&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Trevor McDougall is a world-leading researcher in ocean thermodynamics.</span>
<span class="attribution"><span class="source">Supplied</span></span>
</figcaption>
</figure>
<p>A world-leading authority on ocean mixing, McDougall was recognised for his many contributions, including a redefinition of the thermodynamic description of seawater. The latter <a href="https://csiropedia.csiro.au/science-adopts-a-new-definition-of-seawater/">was accepted by</a> the Intergovernmental Oceanographic Commission in 2009 as a new international standard. </p>
<p>“To receive the Prime Minister’s Prize for Science is an incredible honour, and it’s also an honour for the early career researchers that I’ve been working with for the past ten years,” said McDougall.</p>
<p>“They’ve been integral to some of the results that have been recognised in this prize.” </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/the-ocean-is-becoming-more-stable-heres-why-that-might-not-be-a-good-thing-157911">The ocean is becoming more stable – here's why that might not be a good thing</a>
</strong>
</em>
</p>
<hr>
<h2>Predicting sea level rise</h2>
<p>Earth’s oceans and their role in climate change are also the focus of another prize recipient this year – physical oceanographer and ocean modeller Dr Adele Morrison from the Australian National University (ANU). </p>
<p>She won the Malcolm McIntosh Prize for Physical Scientist of the Year for her innovative methods of modelling ocean circulation around Antarctica.</p>
<p>Morrison’s research has greatly reduced uncertainty in predicting future sea level rise from Antarctic ice sheet melt, driven by warm ocean currents in the Southern Ocean.</p>
<figure class="align-center ">
<img alt="A smiling woman with curly hair looking at the camera with greenery in the background" src="https://images.theconversation.com/files/496391/original/file-20221121-18-9zfgta.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/496391/original/file-20221121-18-9zfgta.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/496391/original/file-20221121-18-9zfgta.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/496391/original/file-20221121-18-9zfgta.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/496391/original/file-20221121-18-9zfgta.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/496391/original/file-20221121-18-9zfgta.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/496391/original/file-20221121-18-9zfgta.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Adele Morrison’s work has revealed the ongoing impact of warm ocean currents on Antarctic ice melt.</span>
<span class="attribution"><span class="source">Supplied</span></span>
</figcaption>
</figure>
<p>Such work is particularly pertinent to Australia, with 85% of Australians living in places that could soon be affected by rising sea levels.</p>
<p>Morrison hopes to “inspire the next generation of scientists to unravel new discoveries and technologies that limit the impacts of climate change and our transition to a zero-emissions world”.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/satellites-reveal-ocean-currents-are-getting-stronger-with-potentially-significant-implications-for-climate-change-159461">Satellites reveal ocean currents are getting stronger, with potentially significant implications for climate change</a>
</strong>
</em>
</p>
<hr>
<h2>Molecular diagnostics and solar cell improvements also recognised</h2>
<p>Several other researchers and inventors received accolades at the ceremony held on November 21 at Parliament House in Canberra.</p>
<ul>
<li><p>Adjunct Professor Alison Todd and Dr Elisa Mokany, co-founders of the molecular diagnostics company SpeeDx, received the Prize for Innovation. Their highly advanced diagnostic tests have improved diagnosis and treatments for several infectious diseases and cancers.</p></li>
<li><p>The other Prize for Innovation went to Dr Nick Cutmore, Dr James Tickner and Mr Dirk Treasure of the company Chrysos. They have successfully commercialised an X-ray technology that measures the presence of gold and minerals in ore samples.</p></li>
<li><p>Professor Si Ming Man from ANU was awarded the Frank Fenner Prize for Life Scientist of the Year for his work on inflammation and new therapies for inflammatory diseases.</p></li>
<li><p>The Prize for New Innovators went to University of Melbourne’s Dr Pip Karoly, whose unique seizure forecasting technology is improving the lives of millions of people with epilepsy.</p></li>
<li><p>UNSW Associate Professor Brett Hallam was also awarded the Prize for New Innovators, whose discoveries and patented tech have improved solar cell performance by a whopping 10%.</p></li>
</ul>
<h2>Inspiring our youngest future scientists</h2>
<p>Each year, the prizes also include recognition for outstanding achievements in science teaching.</p>
<p>Mr George Pantazis from Marble Bar Primary School in Western Australia was awarded the Prize for Excellence in Science Teaching in Primary Schools for his work integrating First Nations cultural knowledge, including the critically endangered Nyamal language, in the school’s science, technology, engineering, and mathematics (STEM) program.</p>
<p>This “wouldn’t be possible without the support of our teachers and the community, in particular the Nyamal people and their Elders”, said Pantazis.</p>
<p>“This prize is the highlight of my career. I owe it all to the students. Without them, I have nothing.”</p>
<p>The Prize for Excellence in Science Teaching in Secondary Schools went to Ms Veena Nair from Viewbank College, Victoria. She has collaborated with countless academics and industry leaders to not only show students the practical application of STEAM (science, technology, engineering, arts and mathematics) subjects, but also find pathways for them in STEAM careers.</p>
<p>“As a first-generation migrant, I’m deeply thankful to my birth country India, where I got my foundation skills – and to my adopted country Australia, where I was given the wings to fly,” said Nair.</p>
<p>For 23 years now, the Prime Minister’s Science Prizes have been awarded for outstanding achievements in scientific research, research-based innovation and excellence in science teaching. The recipients share a prize pool of $750,000.</p>
<p>This is the first year since 2019 the prizes were held at the Parliament House again, with the 2020 and 2021 events having taken place virtually.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/explainer-whats-the-difference-between-stem-and-steam-95713">Explainer: what's the difference between STEM and STEAM?</a>
</strong>
</em>
</p>
<hr>
<img src="https://counter.theconversation.com/content/195015/count.gif" alt="The Conversation" width="1" height="1" />
The 2022 Prime Minister’s Science Prizes have been awarded for outstanding achievements in scientific research, innovation and teaching.Signe Dean, Science + Technology Editor, The ConversationLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1947672022-11-18T17:18:09Z2022-11-18T17:18:09ZThe risk of seizures and epilepsy is higher after COVID than after the flu – new research<figure><img src="https://images.theconversation.com/files/495707/original/file-20221116-26-kgd3xh.jpg?ixlib=rb-1.1.0&rect=0%2C26%2C4500%2C2964&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/closeup-ct-scan-67-year-old-473967136">hutpaza/Shutterstock</a></span></figcaption></figure><p>Epilepsy is one of the most common neurological disorders, affecting roughly <a href="https://www.who.int/publications/i/item/epilepsy-a-public-health-imperative">50 million people</a> around the world. It’s a condition characterised by seizures which involve episodic, abnormal activity in nerve cells in the brain. </p>
<p>People can have convulsive seizures, where the body stiffens and shakes. There are also more subtle seizures during which people may, for example, lose awareness for short periods of time. While epilepsy always involves seizures, some people can have seizures without being diagnosed with epilepsy.</p>
<p>Epilepsy is more common <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)33064-8/fulltext">as we get older</a>, and the main risk factor for the condition in later life is stroke. Given that COVID affects older adults most severely and <a href="https://pubmed.ncbi.nlm.nih.gov/33879319/">can result in stroke</a>, some might speculate that COVID could see more people develop epilepsy. Whether this is actually the case, though, has been difficult to prove. </p>
<p>In <a href="https://n.neurology.org/content/early/2022/11/16/WNL.0000000000201595">a new study</a>, we’ve found that the risk of seizures or epilepsy following a COVID infection is significantly higher than after an influenza infection.</p>
<p>We know that COVID is associated with psychiatric and neurological symptoms <a href="https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(21)00084-5/fulltext">such as anxiety</a> and <a href="https://www.science.org/doi/10.1126/science.abm2052">difficulty with memory</a>. Many early studies exploring the impact of COVID on the brain, however, focused on the immediate period after infection or had low patient numbers.</p>
<p>To try to more definitively answer whether COVID is associated with epilepsy or seizures, we looked at the health records of people who had been infected with COVID. We then carefully matched them (so that they were similar in characteristics like age, sex and medical conditions) with a group of people who had been infected with influenza. </p>
<p>Each group consisted of 152,754 people, none of whom had previously been diagnosed with epilepsy or recurrent seizures. We compared the incidence of epilepsy and seizures between the two groups over a six month period following the initial infection. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/covid-19s-impacts-on-the-brain-and-mind-are-varied-and-common-new-research-161215">COVID-19's impacts on the brain and mind are varied and common – new research</a>
</strong>
</em>
</p>
<hr>
<h2>What we found</h2>
<p>The rate of new cases of epilepsy or seizures was 0.94% in the people who had COVID, compared with 0.6% in those who had influenza. While the overall risk of seizures is therefore small, these cases show that people who had COVID were 55% more likely to develop epilepsy or seizures over the next six months than people who had influenza.</p>
<p>We then looked to see if certain groups were particularly susceptible to seizures or epilepsy after COVID. We found that, compared to influenza, children aged under 16 and people who were not hospitalised were more likely to develop epilepsy or seizures.</p>
<p>There was also a delay to when children and non-hospitalised patients experienced seizures or epilepsy, perhaps explaining why this phenomenon has not been detected in studies of shorter duration.</p>
<p>Severe infections can make people more susceptible to seizures, so it’s possible that if someone is hospitalised for either COVID or the flu that seizures will manifest as part of the acute illness.</p>
<figure class="align-center ">
<img alt="Three children walking in a forrest." src="https://images.theconversation.com/files/495714/original/file-20221116-12-11pzf8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/495714/original/file-20221116-12-11pzf8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/495714/original/file-20221116-12-11pzf8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/495714/original/file-20221116-12-11pzf8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/495714/original/file-20221116-12-11pzf8.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/495714/original/file-20221116-12-11pzf8.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/495714/original/file-20221116-12-11pzf8.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The increased risk was more noticeable in children than adults.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/children-having-fun-balancing-on-tree-389052964">Monkey Business Images/Shutterstock</a></span>
</figcaption>
</figure>
<p>We see this in our data. For people with COVID who were hospitalised, the point at which a diagnosis of seizures or epilepsy was most common was at nine days after infection. For those who were not hospitalised, the peak was at 41 days. </p>
<p>In children with COVID, the peak point for seizures or epilepsy was at 50 days after infection and at that time children who had COVID were three times more likely to have epilepsy or seizures than children who had flu.</p>
<p>It’s possible that seizures occur due to changes in the immune system which may take some weeks to manifest, thereby contributing to this delay. But we don’t know why seizures might happen after COVID, nor why their onset appears to be delayed after an infection in children and patients with less severe disease.</p>
<p>Most people who have a stroke while infected with COVID will be hospitalised. So it doesn’t seem that stroke is the explanation for the relative increase in post-COVID seizures seen in adults, given we saw an increase among non-hospitalised patients too.</p>
<h2>What now?</h2>
<p>Although the overall rate of seizures and epilepsy after COVID is small, given the large number of people who have been infected with COVID, this could result in increases in the number of people with seizures and epilepsy.</p>
<p>Our study also demonstrates that even relatively milder COVID infections can be associated with neurological conditions, and shows the need for vaccination programmes that try to prevent COVID infection, perhaps especially in children. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/we-studied-how-covid-affects-mental-health-and-brain-disorders-up-to-two-years-after-infection-heres-what-we-found-188918">We studied how COVID affects mental health and brain disorders up to two years after infection – here's what we found</a>
</strong>
</em>
</p>
<hr>
<p>There are some limitations to this study. For example, we didn’t know which variant of COVID people were infected with or whether they had been vaccinated.</p>
<p>We now need to do more research to try and understand why people may be developing epilepsy and having seizures following COVID. It will also be vital to continue to pool data on the neurological consequences of COVID and track longer-term trajectories of people who do develop seizures following a COVID infection.</p><img src="https://counter.theconversation.com/content/194767/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>This study was supported by the National Institute for Health and Care Research (NIHR) Oxford Health Biomedical Research Centre (BRC), grant BRC-1215-20005</span></em></p>People who had COVID were 55% more likely to develop epilepsy or seizures over the next six months than people who had influenza – but the overall risk is still small.Arjune Sen, Head of the Oxford Epilepsy Research Group, University of OxfordLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1938192022-11-07T12:34:36Z2022-11-07T12:34:36ZEpilepsy: gene therapy technique targeting overactive brain cells shows promise in treating drug-resistant form of the condition<figure><img src="https://images.theconversation.com/files/493789/original/file-20221107-13-i4n7qr.jpg?ixlib=rb-1.1.0&rect=26%2C0%2C3500%2C1996&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Epileptic seizures are caused by brain cells becoming overactive.
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/neuronal-network-electrical-activity-neuron-cells-1691666992">MattLphotography/ Shutterstock</a></span></figcaption></figure><p>Something like <a href="https://www.who.int/news-room/fact-sheets/detail/epilepsy">50 million people worldwide</a> have epilepsy. While the majority of these people are able to use medications to manage and prevent their seizures, around one-third don’t respond well to these treatments. In such cases, the only option available to bring seizures under control is to <a href="https://epilepsysociety.org.uk/about-epilepsy/treatment/epilepsy-and-brain-surgery">remove the part of the brain</a> where seizures arise. But this procedure is extremely risky.</p>
<p>Since epileptic seizures are caused by excessive activity of brain cells (neurons) in specific parts of the brain, being able to target these neurons and turn them off could very well prevent seizures from happening.</p>
<p>Using an innovative new gene therapy approach we have developed, we were able to show in cell and animal models that it is possible to <a href="https://www.science.org/doi/epdf/10.1126/science.abq6656">specifically target the neurons</a> that cause epileptic seizures. This subsequently prevented them from becoming overactive and causing seizures in the future. </p>
<p>This discovery not only has major implications for treating drug-resistant epilepsy, but there’s a chance it may also be used to treat other neurological conditions caused by overactive neurons, including Parkinson’s disease and migraines.</p>
<h2>Gene therapy</h2>
<p>Gene therapy works by directly altering a person’s genes in order to treat a disease or condition. There are a few different ways of doing this.</p>
<p><a href="https://www.jneurosci.org/content/early/2019/02/12/JNEUROSCI.1143-18.2019?versioned=true">Previous studies</a> that have used gene therapy to treat epilepsy in animal models have done this by using a virus that has been altered in the lab so it’s no longer harmful. Researchers would inject the virus into the brain region where seizures occur. The virus would then implant stretches of DNA into the cells, effectively modulating the way they worked – <a href="https://www.nature.com/articles/s41591-018-0103-x">making them less active</a> and preventing seizures.</p>
<p>While this technique is far less invasive than brain surgery, the problem with the method is that it affects all the neurons in the brain region – not just those causing the seizures. It also permanently alters the properties of the cells that take up the virally delivered DNA, which can permanently modify brain function. </p>
<p>But our innovative new gene therapy tool has shown it’s possible to alter only the brain cells that cause seizures, leaving nearby healthy neurons unaffected. We were able to do this by taking advantage of how gene expression is normally regulated.</p>
<figure class="align-center ">
<img alt="An image of multiple DNA strands." src="https://images.theconversation.com/files/493795/original/file-20221107-3705-r3aoea.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/493795/original/file-20221107-3705-r3aoea.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/493795/original/file-20221107-3705-r3aoea.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/493795/original/file-20221107-3705-r3aoea.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/493795/original/file-20221107-3705-r3aoea.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/493795/original/file-20221107-3705-r3aoea.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/493795/original/file-20221107-3705-r3aoea.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Our new gene therapy tool targeted the body’s promoters.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/dna-molecule-macro-blue-string-on-775854724">SynthEx/ Shutterstock</a></span>
</figcaption>
</figure>
<h2>The role of promoters</h2>
<p>The 20,000 or so genes we have in our body each contain instructions to make different proteins and molecules. These genes are typically under the control of neighbouring stretches of DNA, called promoters. These determine whether and how much of a particular protein is made. Different cells express different proteins depending on which promoters are active or inactive.</p>
<p>There’s also a special type of promoter (called “activity-dependent” promoters) that will only switch on in response to biochemical signals made by neurons when they fire intensely – such as during a seizure. We took advantage of these activity-dependent promoters, creating a gene therapy that senses and turns down the excitability of neurons that cause seizures. We did this by coupling activity-dependent promoters to DNA sequences that contain proteins which calm down neurons.</p>
<p>We initially tested the gene therapy tool in neurons grown in a dish, and then in mice that had drug-resistant epilepsy. We also tested this technique in lab-grown human “mini brains”. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/scientists-grow-brain-tissue-with-different-regions-in-lab-17560">Scientists grow brain tissue with different regions in lab</a>
</strong>
</em>
</p>
<hr>
<p>In each test, we were able to show this new gene therapy technique was effective in calming down the overactive neurons involved in seizures, while leaving healthy bystander cells unaffected.</p>
<p>Although it takes an hour or so to switch on – longer than the typical duration of a seizure – the new gene therapy is highly effective in preventing subsequent seizures. It does this by automatically selecting which neurons to treat and switching them off. It’s also able to return neurons to their original state when brain activity returns to normal. If seizures occur again, the promoter is ready to switch on. </p>
<p>The treatment therefore only has to be given once, but has a lasting effect – possibly lifelong. Importantly, the treatment did not affect the performance of the mice in tests of memory and other normal behaviour (such as their anxiety levels, learning and mobility).</p>
<p>We are excited by the breakthrough, because it could in principle bring the prospect of gene therapy to a wide range of people with drug-resistant epilepsy. But before the therapy is ready to use with these patients, we will need to put it through a number of tests to verify that it can be scaled up to larger brains.</p><img src="https://counter.theconversation.com/content/193819/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Gabriele Lignani consults to/owns shares in a company that aims to bring epilepsy gene therapy to the clinic. He received funding from Epilepsy Research UK and Medical Research Council. </span></em></p><p class="fine-print"><em><span>Dimitri Kullmann consults to/owns shares in a company that aims to bring epilepsy gene therapy to the clinic. He received funding from the Wellcome Trust and the Medical Research Council.</span></em></p>This technique could also be applied to other conditions, such as Parkinson’s disease.Gabriele Lignani, Associate Professor, Clinical & Experimental Epilepsy, UCLDimitri Kullmann, Professor of Neurology, UCLLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1889182022-08-18T14:12:07Z2022-08-18T14:12:07ZWe studied how COVID affects mental health and brain disorders up to two years after infection – here’s what we found<figure><img src="https://images.theconversation.com/files/479704/original/file-20220817-8116-s4twhd.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C5991%2C3988&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">COVID has been linked with a higher rate of psychiatric and neurological disorders.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/hands-holding-brain-puzzle-paper-cutout-1814268452">SewCream/Shutterstock</a></span></figcaption></figure><p>The occurrence of mental health conditions and neurological disorders among people recovering from COVID has been a concern since early in the pandemic. Several studies have shown that a <a href="https://www.sciencedirect.com/science/article/pii/S2215036621000845">significant proportion</a> of adults <a href="https://www.thelancet.com/journals/lanpub/article/PIIS2468-2667(22)00042-1/fulltext">face problems</a> of this kind, and that the risks are greater than following other infections.</p>
<p>However, several questions remain. Do the risks of psychiatric and neurological problems dissipate, and if so, when? Are the risks similar in children as in adults? Are there differences between COVID variants? </p>
<p>Our new study, published in <a href="https://www.thelancet.com/journals/lanpsy/article/PIIS2215-0366(22)00260-7/fulltext">The Lancet Psychiatry</a>, explored these issues. In analyses led by my colleague Maxime Taquet, we used the electronic health records of about 1.25 million people diagnosed with COVID, mostly from the US. We tracked the occurrence of 14 major neurological and psychiatric diagnoses in these patients for up to two years. </p>
<p>We compared these risks with a closely matched control group of people who had been diagnosed with a respiratory infection other than COVID. </p>
<p>We examined children (aged under 18), adults (18-65) and older adults (over 65) separately.</p>
<p>We also compared people who contracted COVID just after the emergence of a new variant (notably omicron, but earlier variants too) with those who did so just beforehand.</p>
<p>Our findings are a mixture of good and bad news. Reassuringly, although we observed a greater risk of common psychiatric disorders (anxiety and depression) after COVID infection, this heightened risk rapidly subsided. The rates of these disorders among people who had COVID were no different from those who had other respiratory infections within a couple of months, and there was no overall excess of these disorders over the two years.</p>
<p>It was also good news that children were not at greater risk of these disorders at any stage after COVID infection. </p>
<p>We also found that people who had had COVID were not at higher risk of getting Parkinson’s disease, which had been a concern early in the pandemic.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/covid-long-lasting-symptoms-rarer-in-children-than-in-adults-new-research-165701">COVID: long-lasting symptoms rarer in children than in adults – new research</a>
</strong>
</em>
</p>
<hr>
<p>Other findings were more worrying. The risks of being diagnosed with some disorders, such as psychosis, seizures or epilepsy, brain fog and dementia, though mostly still low, remained elevated throughout the two years after COVID infection. For example, the risk of dementia in older adults was 4.5% in the two years after COVID compared with 3.3% in those with another respiratory infection.</p>
<p>We also saw an ongoing risk of psychosis and seizures in children.</p>
<figure class="align-center ">
<img alt="A woman sits by a window, hiding her head." src="https://images.theconversation.com/files/479705/original/file-20220817-11701-ygfp4m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/479705/original/file-20220817-11701-ygfp4m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=338&fit=crop&dpr=1 600w, https://images.theconversation.com/files/479705/original/file-20220817-11701-ygfp4m.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=338&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/479705/original/file-20220817-11701-ygfp4m.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=338&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/479705/original/file-20220817-11701-ygfp4m.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=424&fit=crop&dpr=1 754w, https://images.theconversation.com/files/479705/original/file-20220817-11701-ygfp4m.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=424&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/479705/original/file-20220817-11701-ygfp4m.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=424&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Rates of depression and anxiety were higher after COVID, but only for a short time.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/beautiful-young-blonde-caucasian-female-feeling-2057071157">Stock Unit/Shutterstock</a></span>
</figcaption>
</figure>
<p>In terms of variants, although our data confirms that omicron is a much milder illness than the previous delta variant, survivors remained at similar risk of the neurological and psychiatric conditions we looked at. </p>
<p>However, given how recently omicron emerged, the data we have for people who were infected with this variant only goes up to about five months after infection. So the picture may change.</p>
<h2>Mixed results</h2>
<p>Overall, our study reveals a mixed picture, with some disorders showing a transient excess risk after COVID, while other disorders have a sustained risk. For the most part, the findings are reassuring in children, but with some concerning exceptions. </p>
<p>The results on omicron, the variant currently dominant around the world, indicate that the burden of these disorders is likely to continue, even though this variant is milder in other respects.</p>
<p>The study has important caveats. Our findings don’t capture people who may have had COVID but it wasn’t documented in their health records – perhaps because they didn’t have symptoms. </p>
<p>And we cannot fully account for the effect of vaccination, because we didn’t have complete information about vaccination status, and some people in our study caught COVID before vaccines became available. That said, in <a href="https://pubmed.ncbi.nlm.nih.gov/35447302/">a previous study</a> we showed the risks of these outcomes were pretty similar in people who caught COVID after being vaccinated, so this might not have significantly affected the results.</p>
<p>Also, the risks observed in our study are relative to people who had had other respiratory infections. We don’t know how they compare to people without any infection. We also don’t know how severe or long lasting the disorders were. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/how-does-covid-affect-the-brain-two-neuroscientists-explain-164857">How does COVID affect the brain? Two neuroscientists explain</a>
</strong>
</em>
</p>
<hr>
<p>Finally, our study is observational and so cannot explain how or why COVID is associated with these risks. Current theories include persistence of the virus in the nervous system, the immune reaction to the infection, or problems with blood vessels. These are being investigated in <a href="https://academic.oup.com/braincomms/advance-article/doi/10.1093/braincomms/fcac206/6668727?searchresult=1">separate research</a>.</p><img src="https://counter.theconversation.com/content/188918/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Paul Harrison receives funding from the National Institute for Health and Care Research, MQ, and The Wolfson Foundation. </span></em></p>People who get COVID continue to face increased risks of developing some neurological and psychiatric conditions, like psychosis and dementia, for up to two years afterwards.Paul Harrison, Professor of Psychiatry, University of OxfordLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1886102022-08-12T09:57:04Z2022-08-12T09:57:04ZEpilepsy: how an AI algorithm detects related brain abnormalities – new research<figure><img src="https://images.theconversation.com/files/478787/original/file-20220811-23-h5237v.jpg?ixlib=rb-1.1.0&rect=17%2C26%2C5912%2C3920&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Up to a third of epilepsy cases are drug-resistant.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/blured-photo-woman-suffering-vertigo-dizziness-2122756115">Shutterstock</a></span></figcaption></figure><p>Around 50 million people worldwide <a href="https://www.who.int/news-room/fact-sheets/detail/epilepsy">have epilepsy</a>. While anti-seizure medications are available and effective for the majority of people with the condition, 20%-30% don’t respond to medications. </p>
<p>Abnormalities in the brain are one of the leading causes of this drug-resistant epilepsy, which is usually identified by MRI scans before surgery is carried out to cure the patient. However, identifying these abnormal areas from MRIs is an ongoing challenge for clinicians, as these scans can look normal. </p>
<p>We wanted to see if an artificial intelligence (AI) algorithm could help find these subtle brain abnormalities (known as focal cortical dysplasia or FCD). Our results, <a href="https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awac224/6659752?searchresult=1">published in the journal Brain</a>, show the AI was successful in detecting abnormalities in two thirds more cases than MRI scans alone. </p>
<h2>How does the AI work?</h2>
<p>To develop a reliable AI algorithm you need to train it on examples from a wide variety of patients. </p>
<p>Individual epilepsy surgery centres typically treat only small numbers of patients each year with this abnormality, so we created the <a href="https://meldproject.github.io/#:%7E:text=The%20Multi%2Dcentre%20Epilepsy%20Lesion%20Detection%20(MELD)%20project%20is,patients%20with%20drug%2Dresistant%20epilepsy">Multicentre Epilepsy Lesion Detection project</a> (MELD) to collect over 1,000 MRI scans from 22 centres across the world. We then used this data to train an AI algorithm to detect these abnormalities. </p>
<figure class="align-center ">
<img alt="MRI brain scans" src="https://images.theconversation.com/files/478785/original/file-20220811-26-kx5p7s.jpg?ixlib=rb-1.1.0&rect=20%2C13%2C4459%2C2930&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/478785/original/file-20220811-26-kx5p7s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/478785/original/file-20220811-26-kx5p7s.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/478785/original/file-20220811-26-kx5p7s.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/478785/original/file-20220811-26-kx5p7s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/478785/original/file-20220811-26-kx5p7s.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/478785/original/file-20220811-26-kx5p7s.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">MRI scans can show abnormalities, but our AI is better at identifying them.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/mri-examination-film-patients-head-medical-1096788182">Shutterstock</a></span>
</figcaption>
</figure>
<p>To develop the algorithm, we quantified features from the MRI scans, such as how thick or folded the brain surface was, and measured these at around 300,000 locations in each participant’s brain. </p>
<p>Expert radiologists in our team then labelled areas on the MRI scans as either being healthy or abnormal. We then trained the algorithm to recognise patterns of features that characterise this particular FCD brain abnormality. </p>
<p>We found that, overall, our algorithm was able to detect these abnormalities in 67% of patients. A third of patients had previously had their MRI scans reported as normal – the brain abnormality had been missed by radiologists. </p>
<p>Despite these lesions being particularly challenging to see by eye, the algorithm was still able to detect 63% of them in this third of patients. This is particularly important, as if doctors can find the abnormality in the brain scan, then surgery to remove it can provide a cure. </p>
<h2>Black boxes</h2>
<p>One common problem with AI algorithms is that they are “black boxes”, meaning they learn patterns from data rather than being explicitly programmed to make decisions. This can make it difficult to understand how they make these decisions. </p>
<p>We put an emphasis on creating an AI algorithm with predictions that could be interpreted, through calculating which features contributed most to the final prediction. The information the algorithm used is summarised into a report that highlights where in the brain the AI thought was abnormal and why. </p>
<p>The AI algorithm is not perfect, and one key step when incorporating this type of technology into clinical practice is confirming whether the AI’s findings are true brain abnormalities or due to MRI artefacts. For example, MRI scan quality is often not the best and can be affected by the patient moving in the scanner, which results in the image being unclear and blurred. </p>
<p>The reports therefore need to be considered alongside other investigations that patients undergo as part of planning their epilepsy surgery. </p>
<p>Excitingly, a number of epilepsy surgery hospitals are now using the MELD algorithm in this way. We have begun collecting more data, from a wider number of causes of epilepsy, which will be used to create more powerful diagnostic AI algorithms.</p>
<p>Our study on FCD detection uses the largest MRI cohort of FCDs to date, meaning it is able to detect all types of these abnormalities. The algorithm can be run by hospitals around the world on any patient with a suspicion of having an FCD who is over the age of three and has an MRI scan. To give one snapshot, around 440 children a year in England could benefit from epilepsy surgery. </p>
<p>The MELD algorithm could help to find more hidden lesions in children and adults with epilepsy, and enable more people with epilepsy to be considered for brain surgery that could cure their epilepsy and improve their cognitive development.</p><img src="https://counter.theconversation.com/content/188610/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>This project was supported by the Rosetrees Trust, Konrad Wagstyl funded by the Wellcome Trust. </span></em></p><p class="fine-print"><em><span>Sophie Adler receives funding from the Rosetrees Trust. </span></em></p>AI algorithm that detects brain abnormalities could help cure epilepsy.Konrad Wagstyl, Sir Henry Wellcome Postdoctoral Fellow, Wellcome Centre for Human Neuroimaging, UCLSophie Adler, Research Fellow, Great Ormond Street Institute of Child Health, UCLLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1876072022-08-04T12:22:28Z2022-08-04T12:22:28ZIlluminating the brain one neuron and synapse at a time – 5 essential reads about how researchers are using new tools to map its structure and function<figure><img src="https://images.theconversation.com/files/475765/original/file-20220725-30588-3lzyhd.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1960%2C1527&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The U.S. BRAIN Initiative seeks to elucidate the connection between brain structure and function.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/computer-artwork-of-human-brain-profile-royalty-free-illustration/85757401">Science Photo Library - PASIEKA/Brand X Pictures via Getty Images</a></span></figcaption></figure><p>Scientists know both a lot and very little about the brain. With <a href="https://doi.org/10.48550/arXiv.1906.01703">billions of neurons and trillions of connections</a> among them, and the experimental limitations of examining the seat of consciousness and bodily function, studying the human brain is a technical, theoretical and ethical challenge. And one of the biggest challenges is perhaps one of the most fundamental – seeing what it looks like in action.</p>
<p>The U.S. <a href="https://braininitiative.nih.gov">Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative</a> is a collaboration among the National Institutes of Health, Defense Advanced Research Projects Agency, National Science Foundation, Food and Drug Administration and Intelligence Advanced Research Projects Activity and others. Since its inception in 2013, <a href="https://braininitiative.nih.gov">its goal</a> has been to develop and use new technologies to examine how each neuron and neural circuit comes together to “record, process, utilize, store, and retrieve vast quantities of information, all at the speed of thought.”</p>
<p>Just as <a href="https://theconversation.com/genomic-sequencing-heres-how-researchers-identify-omicron-and-other-covid-19-variants-172935">genomic sequencing</a> enabled the creation of a <a href="https://theconversation.com/the-human-genome-project-pieced-together-only-92-of-the-dna-now-scientists-have-finally-filled-in-the-remaining-8-176138">comprehensive map of the human genome</a>, tools that elucidate the connection between brain structure and function could help researchers answer long-standing questions about how the brain works, both in sickness and in health.</p>
<p>These five stories from our archives cover research that has been funded by or advances the goals of the BRAIN Initiative, detailing a slice of what’s next in neuroscience.</p>
<h2>1. Mapping the brain</h2>
<p>Attempts to map the structure of the brain date back to <a href="https://web.stanford.edu/class/history13/earlysciencelab/body/brainpages/brain.html">antiquity</a>, when philosophers and scholars had only the unaided eye to map anatomy to function. New <a href="https://embryo.asu.edu/pages/golgi-staining-technique">visualization techniques</a> in the 20th century led to the discovery that, just like all the other organs of the body, the brain is composed of individual cells – <a href="https://doi.org/10.1016/j.cub.2006.02.053">neurons</a>.</p>
<p>Now, <a href="https://theconversation.com/mapping-how-the-100-billion-cells-in-the-brain-all-fit-together-is-the-brave-new-world-of-neuroscience-170182">further advances in microscopy</a> that make use of artificial intelligence and genomics have allowed scientists not just to see each individual neuron in the entire brain, but also to identify the connections among them and begin to ascertain their function. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/432261/original/file-20211116-25-1vtphzf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Stitched high-resolution microscopy image of mouse brain." src="https://images.theconversation.com/files/432261/original/file-20211116-25-1vtphzf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/432261/original/file-20211116-25-1vtphzf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/432261/original/file-20211116-25-1vtphzf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/432261/original/file-20211116-25-1vtphzf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/432261/original/file-20211116-25-1vtphzf.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/432261/original/file-20211116-25-1vtphzf.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/432261/original/file-20211116-25-1vtphzf.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Zooming in on this high-resolution image of a mouse brain reveals rectangular lines where individual image tiles were stitched together, each colored dot representing a specific cell type.</span>
<span class="attribution"><a class="source" href="http://kimlab.io">Yongsoo Kim</a>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
</figure>
<p>Neuroscientist <a href="https://scholar.google.com/citations?user=WOQx1ksAAAAJ&hl=en">Yongsoo Kim</a> of Penn State likened this method to a photo mosaic, piecing together areas of the brain that haven’t been charted before. “It’s like building a Google map of the brain,” wrote Kim. “By combining millions of individual street photos, you can zoom in to see each street corner and zoom out to see an entire city.” Creating these high-resolution maps, he wrote, could help scientists develop new theories on how the brain works and lead to better treatments for brain disorders like dementia.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/mapping-how-the-100-billion-cells-in-the-brain-all-fit-together-is-the-brave-new-world-of-neuroscience-170182">Mapping how the 100 billion cells in the brain all fit together is the brave new world of neuroscience</a>
</strong>
</em>
</p>
<hr>
<h2>2. Brain folds and wrinkles</h2>
<p>Another fundamental question researchers have been puzzling over is how the brain develops the bumps and grooves that riddle its surface. Until roughly the <a href="https://doi.org/10.1093%2Fcercor%2Fbhr053">second trimester</a> of fetal development, the human brain is completely smooth.</p>
<p>Scientists have proposed a number of theories on the mechanics of brain folding. One of them, <a href="https://www.jstor.org/stable/1740783">differential tangential growth</a>, posits that folds form because of a mismatch in growth rates between the outer and inner layers of the brain. To ease the forces compressing the outer layer and restore structural stability, the layers buckle and fold.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/WBWJBFRnqwY?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Harvard researchers modeled how folding reduces instability caused by differential growth rates in the brain.</span></figcaption>
</figure>
<p>Biomechanical engineer <a href="https://scholar.google.com/citations?user=ukOZ0BAAAAAJ&hl=en">Mir Jalil Razavi</a> and computer scientist <a href="https://scholar.google.com/citations?user=r6DIjzUAAAAJ&hl=en">Weiying Dai</a> of Binghamton University <a href="https://theconversation.com/brain-wrinkles-and-folds-matter-researchers-are-studying-the-mechanics-of-how-they-form-170194">created models</a> to clarify this theory. They identified other factors that may also be at play, like the number of axons – the part of the neuron that transmits electrical signals – in a particular area. “Our brain models provide a potential explanation for why brains may form abnormally during development, highlighting the important role that the brain’s structure plays in its proper functioning,” they wrote.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/brain-wrinkles-and-folds-matter-researchers-are-studying-the-mechanics-of-how-they-form-170194">Brain wrinkles and folds matter – researchers are studying the mechanics of how they form</a>
</strong>
</em>
</p>
<hr>
<h2>3. Where memories are stored</h2>
<p>Just like the RAM in a computer, memories take up physical space in the brain. Researchers have hypothesized that memories may be stored by <a href="https://doi.org/10.1016/0166-2236(94)90101-5">rearranging the connections, or synapses</a>, among neurons. While this theory has largely been confirmed by observing <a href="https://doi.org/10.1038/37601">changes in the electrical signals</a> neurons produce after memory formation, what triggers these changes has been unclear.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/440053/original/file-20220110-27-14nulz7.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Image of magenta-colored neurons in a live fish brain, with the synapses colored in green" src="https://images.theconversation.com/files/440053/original/file-20220110-27-14nulz7.png?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/440053/original/file-20220110-27-14nulz7.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=766&fit=crop&dpr=1 600w, https://images.theconversation.com/files/440053/original/file-20220110-27-14nulz7.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=766&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/440053/original/file-20220110-27-14nulz7.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=766&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/440053/original/file-20220110-27-14nulz7.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=963&fit=crop&dpr=1 754w, https://images.theconversation.com/files/440053/original/file-20220110-27-14nulz7.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=963&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/440053/original/file-20220110-27-14nulz7.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=963&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Neurons in a live fish brain, with synapses colored green.</span>
<span class="attribution"><span class="source">Zhuowei Du and Don B. Arnold</span>, <a class="license" href="http://creativecommons.org/licenses/by-nc-nd/4.0/">CC BY-NC-ND</a></span>
</figcaption>
</figure>
<p>Biomedical engineer <a href="https://scholar.google.com/citations?user=z040dHgAAAAJ&hl=en">Don Arnold</a> of the University of Southern California and his colleagues took a mapping approach. They <a href="https://theconversation.com/where-are-memories-stored-in-the-brain-new-research-suggests-they-may-be-in-the-connections-between-your-brain-cells-174578">compared 3D maps of zebrafish synapses</a> before and after memory formation – namely, learning to associate a light with an unpleasant stimulus. They found that one brain region gained synapses while another’s were destroyed, indicating that associative memories may be a result of the formation and loss of connections among neurons.</p>
<p>These findings imply that it might one day be possible to treat conditions like PTSD by physically erasing the associative memory linking a harmless trigger with a traumatic experience. More research is needed, and there are obvious ethical considerations to address. “Nevertheless,” Arnold wrote, “it’s tempting to imagine a distant future in which synaptic surgery could remove bad memories.”</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/where-are-memories-stored-in-the-brain-new-research-suggests-they-may-be-in-the-connections-between-your-brain-cells-174578">Where are memories stored in the brain? New research suggests they may be in the connections between your brain cells</a>
</strong>
</em>
</p>
<hr>
<h2>4. Seizures hijack memory pathways</h2>
<p><a href="https://www.epilepsy.com/what-is-epilepsy/understanding-seizures">Seizures</a> are sudden surges of electrical activity in the brain. People who experience temporal lobe seizures are sometimes unable to remember what happened immediately prior. This may be due to disruptions to the circuitry in the hippocampus, the part of the temporal lobe key to memory consolidation.</p>
<p>Neurology researchers <a href="https://scholar.google.com/citations?user=bjrXv58AAAAJ&hl=en&oi=ao">Anastasia Brodovskaya</a> and <a href="https://scholar.google.com/citations?user=nMb-pTcAAAAJ&hl=en">Jaideep Kapur</a> of the University of Virginia hypothesized that seizures can cause memory loss by <a href="https://theconversation.com/seizures-can-cause-memory-loss-and-brain-mapping-research-suggests-one-reason-why-172280">using the same pathways</a> the brain uses to process memories. They mapped the neurons of mice learning to navigate a maze and during induced seizures, finding that both cases activated the same brain circuits.</p>
<p>“Because they use the same brain pathways, seizures can disrupt the memory consolidation process by taking over the circuit,” they wrote. “This meant that seizures can hijack the memory pathways and cause amnesia.”</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/seizures-can-cause-memory-loss-and-brain-mapping-research-suggests-one-reason-why-172280">Seizures can cause memory loss, and brain-mapping research suggests one reason why</a>
</strong>
</em>
</p>
<hr>
<h2>5. What the nose knows</h2>
<p>What the eye can’t see, the nose can for many organisms. From dogs to mosquitoes, many animals behave in ways that allow them to detect and pursue an odor long before its source comes into view.</p>
<p>Scientists <a href="https://scholar.google.com/citations?user=wn_f7y0AAAAJ&hl=en">John Crimaldi</a>, <a href="https://scholar.google.com/citations?user=JEi-fdoAAAAJ&hl=en">Brian Smith</a>, <a href="https://www.bbe.caltech.edu/people/elizabeth-j-hong">Elizabeth Hong</a> and <a href="https://scholar.google.com/citations?user=GpkJjVUAAAAJ&hl=en">Nathan Urban</a> of the <a href="https://www.odor2action.org/">Odor2Action</a> research network use technology to study olfaction, or sense of smell. They <a href="https://theconversation.com/from-odor-to-action-how-smells-are-processed-in-the-brain-and-influence-behavior-173811">trace how the shape of an odor plume</a> informs how it will be detected, how those odor molecules are translated into electrical signals in the brain, and how these electrical signals are reformatted into useful information that influence behavior.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/MyHR6a-zJM0?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">This video from the Wachowiak Lab at the University of Utah shows the activity of the olfactory bulb in a mouse brain. Each odor the mouse is exposed to makes different combinations of neurons light up.</span></figcaption>
</figure>
<p>A better understanding of the olfactory system, they wrote, can lead to the development of <a href="https://doi.org/10.1177%2F0278364908095118">electronic noses</a> that make searching for chemical weapons and disaster victims safer for people and animals. They also believe that examining the olfactory system can help advance study of the brain. “Its relative simplicity is what allows scientists like us to study it from end to end and learn how the brain works as a whole,” they wrote.</p>
<p>While a grand unified theory of the brain still remains elusive, new tools and techniques are helping researchers excavate its hidden depths. As Crimaldi and his team put it, “An exciting future in scientific and medical development, we believe, is right under our noses.”</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/from-odor-to-action-how-smells-are-processed-in-the-brain-and-influence-behavior-173811">From odor to action – how smells are processed in the brain and influence behavior</a>
</strong>
</em>
</p>
<hr>
<p><em>Editor’s note: This story is a roundup of articles from The Conversation’s archives.</em></p><img src="https://counter.theconversation.com/content/187607/count.gif" alt="The Conversation" width="1" height="1" />
From figuring out where memories are stored to how sensory information translates to behavior, new technologies are helping neuroscientists better understand how the brain works.Vivian Lam, Associate Health and Biomedicine EditorLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1847242022-08-02T16:11:03Z2022-08-02T16:11:03ZWhat epilepsy teaches us about diversity and resilience<figure><img src="https://images.theconversation.com/files/476338/original/file-20220727-1405-kljymn.jpg?ixlib=rb-1.1.0&rect=26%2C33%2C4466%2C2957&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Epilepsy is characterized by spontaneous and recurrent seizures, often triggered by stress or visual stimuli.</span> <span class="attribution"><span class="source">(Shutterstock)</span></span></figcaption></figure><p>There is a growing recognition of the importance of equity, diversity and inclusion in society and its institutions. The most progressive, leading-edge organizations consider the diversity of people to be <a href="https://www.canada.ca/en/treasury-board-secretariat/corporate/reports/building-diverse-inclusive-public-service-final-report-joint-union-management-task-force-diversity-inclusion.html">essential to the success, growth, innovation and development of a society</a>.</p>
<p>The benefits of diversity, however, are far from exclusive to human organizations; heterogeneity and variability are design principles central to all complex natural systems, whether they are <a href="https://doi.org/10.1155/2018/3421529">ecological, cellular or genetic networks</a>.</p>
<p>Whether we are talking about an ecosystem, society or the brain, how does this diversity relate to the functioning and stability of a complex system?</p>
<p>As neuroscientists, our interdisciplinary research and clinical work has drawn us to the incredible complexity and richness of the human brain and natural systems. We seek not only to better understand how the brain’s circuitry works, but also to develop new treatments for neurological diseases such as epilepsy.</p>
<h2>Diversity means resilience</h2>
<p><a href="https://tile.loc.gov/storage-services/service/rbc/rbctos/2017gen17473/2017gen17473.pdf">First developed by Darwin</a>, the idea that diversity leads to stability and survival has been <a href="https://www.hindawi.com/journals/complexity/2018/3421529/">debated by scientists from many disciplines for over a century</a>. The ability of natural systems to resist change is a characteristic known as resilience. This fundamental characteristic emerges from interactions between members of the same system — such as species in an ecosystem, individuals in a group or cells in an organism — and enables it to maintain its functions over time.</p>
<p>Resilience is tested by change. Some ecosystems can adapt to the extinction of specific species or to drought. Some virtual communities or social networks can withstand cyberattacks. Some organizations can continue to operate in the wake of conflict, war, political revolution or … pandemic. </p>
<p>In light of these common examples — and many others related to the social or natural sciences — it is now more important than ever to understand the role played by diversity in maintaining the resilience of complex systems.</p>
<p>What if clues to the answer lie in the circuits of the brain, specifically in a brain with epilepsy?</p>
<h2>Tipping over in an electrical storm</h2>
<p>For several years, our interdisciplinary team has been studying epilepsy, <a href="https://doi.org/10.1046/j.1528-1157.43.s.6.1.x">the most common severe neurological disorder</a>. Epilepsy is characterized primarily by the apparently spontaneous and recurrent occurrence of seizures, often triggered by stress or visual stimuli (<a href="https://doi.org/10.1016/j.cub.2017.03.067">such as flashing lights or specific images</a>). Recent research has also shown that <a href="https://doi.org/10.1038/s41467-017-02577-y">the frequency of these seizures can vary with the time of day or month</a>, depending on the individual’s sleep-wake cycle, for example.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/466391/original/file-20220531-22-o8z5oe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="woman holding herself against a wall with one hand and her head with the other while she appears to be having a seizure" src="https://images.theconversation.com/files/466391/original/file-20220531-22-o8z5oe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/466391/original/file-20220531-22-o8z5oe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/466391/original/file-20220531-22-o8z5oe.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/466391/original/file-20220531-22-o8z5oe.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/466391/original/file-20220531-22-o8z5oe.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/466391/original/file-20220531-22-o8z5oe.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/466391/original/file-20220531-22-o8z5oe.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Epilepsy is the most common serious neurological disorder.</span>
<span class="attribution"><span class="source">(Shutterstock)</span></span>
</figcaption>
</figure>
<p>In this light, a brain with epilepsy can be seen as fragile and not resilient, regularly tipping into an electrical storm. Thus, rather than adapting normally to changes, neurons become disproportionately active and synchronous, and the resulting intense electrical activity spreads, disrupting brain function.</p>
<p>Because of the significant impact of these seizures on patients and their families, our team has been relentlessly studying the circuits responsible for triggering them and exploring ways to prevent them.</p>
<p>What does diversity have to do with epilepsy? Our team recently measured the activity of neurons in people with epilepsy. We found that neurons in the brain regions responsible for triggering seizures <a href="https://doi.org/10.1016/j.celrep.2022.110863">were much less diverse than those in regions not responsible for seizures</a>. These neurons were strangely similar to each other, showing highly similar characteristics and responses.</p>
<p>Could this lack of diversity explain why seizure-prone brains are less resilient?</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1529117822298775553"}"></div></p>
<h2>Mathematical models to the rescue</h2>
<p>To answer this complex question, we turned to mathematics. What if, through mathematical models of brain circuitry, we could understand how neural diversity (or the lack thereof) predicts seizure resilience? Could we determine whether neuronal diversity promotes resilience in the brain?</p>
<p>Using our equations, we found that when diversity was too low, seizure-like activity would spontaneously emerge: <a href="https://doi.org/10.1016/j.celrep.2022.110863">the activity of the neurons would become vulnerable to sudden change in synchrony</a>, reminiscent of what we observe during seizures. These results are unequivocal: low diversity made these neuronal circuits fragile, poorly resilient and unable to maintain the type of activity required to preserve brain function.</p>
<p>What do these result mean? They provide key insights about the role played by different types of neurons in maintaining brain function. </p>
<p>These results are helping us look at neurological diseases such as epilepsy differently than we did before, potentially opening up new avenues on how to treat them. Our approach of using interdisciplinary methods and mathematics allows us to go further and understand better how diversity increases resilience, providing invaluable cues and answering hard questions such as: Is there an optimal level of diversity? What are the different types of diversities and do they all promote stability equally? Could we enhance resilience by promoting neuronal diversity through targeted therapeutic interventions?</p>
<p>Most importantly, our results also provide a powerful reminder of the primordial role diversity plays in the robustness of systems in the face of change: which holds true not only for neurons and circuits, but for humans and collectives as well. Variety truly is the spice of life.</p><img src="https://counter.theconversation.com/content/184724/count.gif" alt="La Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jérémie Lefebvre has received funding from the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Canadian Institutes of Health Research (CIHR).</span></em></p><p class="fine-print"><em><span>Taufik A. Valiante has received funding from the Krembil Brain Institute, and the Natural Sciences and Engineering Research Council of Canada (NSERC).</span></em></p>Our team studied the activity of neurons in people with epilepsy. Neurons in the brain regions responsible for triggering seizures were much less diverse.Jérémie Lefebvre, Professeur agrégé de neurosciences computationnelles et neurophysiologie, L’Université d’Ottawa/University of OttawaTaufik A. Valiante, Neurosurgeon/neuroscientist, University of TorontoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1847402022-07-21T12:25:29Z2022-07-21T12:25:29ZSilent, subtle and unseen: How seizures happen and why they’re hard to diagnose<figure><img src="https://images.theconversation.com/files/470665/original/file-20220623-64215-3tfegq.jpg?ixlib=rb-1.1.0&rect=7%2C22%2C5104%2C3380&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Approximately 10% of people will experience at least one seizure during their lifetime.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/brain-and-brain-waves-in-epilepsy-royalty-free-illustration/973895626?adppopup=true">Kateryna Kon/Science Photo Library via Getty Images</a></span></figcaption></figure><p>The dramatic and incapacitating nature of seizures is reflected in the word itself, which derives from the Greek “to take hold” – like an invisible force suddenly grasping someone and controlling their body. This sense of an unknown force has driven many superstitions and misrepresentations of seizures throughout history.</p>
<p>Over the past century, the public’s understanding of seizures has been gleaned mostly from depictions in movies and television, which are often as disturbing as they are inaccurate. While these dramatic representations intensify visual storytelling, they frequently perpetuate stigma and <a href="https://doi.org/10.1111/j.1528-1157.1999.tb00836.x">understate the complexity of seizures</a>. </p>
<p>The truth is, seizures are far more varied than what you see in popular culture. Instead, they are often subtle, silent and unseen.</p>
<p><a href="https://som.ucdenver.edu/Profiles/Faculty/iframeProfile/30305">As a neurologist</a> who focuses on the comprehensive care of people who experience seizures, I subspecialize in the treatment of those with epilepsy. That includes identifying and improving gaps in epilepsy care. Research shows there are many.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/PG12JfJJW9U?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">Epilepsy is a complex condition, but it is also treatable.</span></figcaption>
</figure>
<h2>Why seizures occur</h2>
<p>A seizure is caused by sudden uncontrolled <a href="https://www.cureepilepsy.org/for-patients/understanding/basics/what-is-seizure/?">electrical activity from a group of neurons</a>. This hyperactivity overwhelms the brain’s normal tendency to suppress such abnormal activity on both a cellular and network level. </p>
<p>Not all seizures are indicative of epilepsy. An otherwise normal brain may experience seizures during alcohol withdrawal. Seizure-like events may also occur with an acute decrease in blood flow, which can cause fainting. </p>
<p>Seizures associated with epilepsy, on the other hand, are <a href="https://www.epilepsydiagnosis.org/">unprovoked and often very difficult to predict</a>. A broad spectrum of underlying abnormalities can all lead to the development of epileptic seizures, including brain tumors, infections, strokes, traumatic brain injury, autoimmune conditions, developmental abnormalities and genetic predispositions.</p>
<h2>Seizures are not uncommon</h2>
<p>Approximately 1 in 10 people <a href="https://doi.org/10.1212/WNL.40.8.1163">will experience a seizure</a> during their lifetime. But only those with a risk of recurrent unprovoked seizures are <a href="https://doi.org/10.1111/epi.13670">considered to have epilepsy</a>, which represents about <a href="https://doi.org/10.1111/J.1528-1157.1993.TB02586.X">1 in 26 people</a></p>
<p>Because of the wide variety of symptoms, substantial <a href="https://doi.org/10.1007/s11910-021-01161-8">delays to diagnosis and treatment</a> can happen. When unrecognized and untreated, seizures worsen over time and lead to <a href="https://doi.org/10.1016/j.yebeh.2015.10.020">decreased quality of life</a>, <a href="https://doi.org/10.1111/epi.16707">cognitive impairments</a>, <a href="https://doi.org/10.1111/j.1528-1157.1995.tb01660.x">injuries, including motor vehicle accidents</a>, and <a href="https://doi.org/10.1093/brain/awt117">sometimes death</a>. </p>
<p>The irony is, much of the suffering is unnecessary. Most people with epilepsy <a href="https://doi.org/10.1111/j.1528-1167.2009.02481.x">can be seizure-free</a> through the use of an inexpensive medication.</p>
<h2>Focal seizures</h2>
<p>Regardless of the cause, <a href="https://doi.org/10.1111/j.1528-1167.2009.02481.x">focal seizures</a> are the most common type found in adults. This seizure type arises from hyperactivation of a confined brain region. For instance, a seizure arising from the left motor cortex of the brain may result in shaking of the right arm. A seizure arising from the visual cortex may cause a person to see flashes of light or other strange visual phenomena. </p>
<p>The most common brain region for focal seizures to arise is one of the temporal lobes, of which there are two – one on either side of the brain. These lobes serve many functions and are involved in vocal, auditory and visual processing, as well as emotions and memory. This is why seizures arising from these areas can lead to a variety of unusual symptoms.</p>
<p>Frequently, focal temporal lobe seizures are relatively subtle, particularly to witnesses. Sometimes they are comprised of purely unusual internal sensations such as sudden intense fear, a sudden sense of déjà vu or possibly a strong odor. Until a seizure spreads to involve more areas of the brain, it may not cause loss of consciousness or convulsions.</p>
<p>Because untreated seizures become more frequent and severe over time, it is not uncommon for epilepsy to begin with these relatively subtle focal seizures, then worsen as the seizures begin to involve more brain tissue, and eventually progress to convulsions.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/W_uXaXwVQ4c?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">People affected by epilepsy discuss the myths surrounding the condition.</span></figcaption>
</figure>
<h2>Delays in diagnosis</h2>
<p>A patient of mine described having strange symptoms for over a decade – symptoms he had not discussed before with me or anyone else. He described recurrent, sudden-onset euphoric sensations, which progressed to an inability to speak for one to two minutes. A bystander would think he was just staring into space. Over the years, these sensations increased in frequency. They eventually became more severe and led to loss of consciousness. </p>
<p>After the patient began an anti-seizure medication regimen, the sensations went away, and he reported improvements in both memory and cognition. Fortunately, he did not experience physical injury, or worse, before his evaluation. But many people are not so lucky.</p>
<p>Recent studies have confirmed that <a href="https://doi.org/10.1002/epi4.12443">delays in diagnosis are common</a> among people who have epilepsy. Undoubtedly, this is because the early subtle and unusual symptoms are not well recognized by patients, families or medical professionals. </p>
<h2>A revealing study</h2>
<p><a href="http://www.humanepilepsyproject.org/">The Human Epilepsy Project</a> is a large, multinational prospective study that followed nearly 500 people with newly treated focal epilepsy for five years. I was among the researchers who analyzed the study’s data, and we found a striking diagnostic delay among many participants. Many of them experienced seizures for <a href="https://doi.org/10.1111/epi.16707">several months or even several years before diagnosis</a>. </p>
<p>From those first seizures to the diagnosis, half the participants experienced injuries; 5% had car accidents attributable to seizures. Extrapolating this data to the general population suggests that every year in the U.S., over 1,800 motor vehicle accidents are due to <a href="https://doi.org/10.1111/epi.16707">undiagnosed subtle focal seizures</a>. With a timely diagnosis, these accidents are potentially preventable.</p>
<p>However, even those evaluated for seizures don’t always receive the correct diagnosis or treatment. Nearly two-thirds of those participating in the Human Epilepsy Project sought an initial seizure evaluation in an emergency department. About 90% were there only after their first convulsive seizure – that is, after the seizure spread and now involved the full brain. </p>
<p>But leading up to that first convulsive seizure, nearly half of participants had been experiencing nonmotor focal seizures, which went largely unrecognized. For that reason, many people who <a href="https://doi.org/10.1111/acem.14114">could have been diagnosed with epilepsy</a> and started on treatment were not. </p>
<p>As it stands now, about 200,000 U.S. adults <a href="https://doi.org/10.1111/j.1528-1167.2008.01443.x">seek evaluation at a hospital’s emergency department</a> for a first lifetime seizure every year. Often, they are diagnosed with epilepsy at that time or shortly thereafter. Poor recognition of subtle seizures bears significant consequences for individuals, communities and the health care system. Improving our understanding of the diverse ways seizures arise and affect lives will help us close the gap and lessen the consequences.</p><img src="https://counter.theconversation.com/content/184740/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jacob Pellinen receives funding in the form of grants from the University of Colorado Department of Neurology, NIH/NCATS Colorado CTSA Grant Number UL1 TR002535, and from the American Epilepsy Society.</span></em></p>Because some seizures are relatively subtle, they can go unrecognized, leading to a delay in diagnosis.Jacob Pellinen, Assistant Professor of Neurology, University of Colorado Anschutz Medical CampusLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1843132022-06-15T20:01:56Z2022-06-15T20:01:56ZTime in hospital sets back tens of thousands of children’s learning each year, but targeted support can help them catch up<figure><img src="https://images.theconversation.com/files/468635/original/file-20220614-18-r7p1do.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C4718%2C3147&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p><a href="https://www.nap.edu.au/">NAPLAN</a> scores can tell us about a child’s learning, but can they also help us to support learners who have had a serious injury or a long-term chronic illness like asthma or epilepsy? </p>
<p>Children who spend time in hospital for these reasons miss out on time in class and are at risk of performing below the <a href="https://www.nap.edu.au/results-and-reports/how-to-interpret/standards">national minimum standard</a> (NMS) in numeracy and literacy as measured by NAPLAN. A serious injury or chronic illness can have a cumulative effect, resulting in lower educational performance, non-completion of high school, and potentially limiting their social, educational and later employment opportunities. </p>
<p>Knowing these risks in advance means parents and educators can plan to support children before the shock of poor school or NAPLAN results. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/every-teacher-needs-to-be-a-literacy-teacher-but-thats-not-happening-in-most-australian-schools-184557">Every teacher needs to be a literacy teacher – but that's not happening in most Australian schools</a>
</strong>
</em>
</p>
<hr>
<p>Serious injury, asthma, mental health, epilepsy and diabetes impact more than a million children each year. More than 100,000 end up in hospital. </p>
<p>We compared their NAPLAN results with kids of the same age and gender who lived in the same area but who had not been hospitalised for those conditions. We found spending time in hospital for these conditions did set back learning, with the exception of type 1 diabetes. </p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1450099372927164422"}"></div></p>
<h2>What did the study find?</h2>
<p><strong>Injury</strong></p>
<p>About <a href="https://doi.org/10.1186/s12887-021-02891-x">70,000 people</a> under the age of 16 are hospitalised with an injury each year in Australia. This can disrupt their ability to attend school or concentrate and learn. </p>
<p>Recovery from injury can be unpredictable. Some young people may fully recover. Others experience ongoing difficulties at school.</p>
<p><a href="https://doi.org/10.1186/s12887-021-02891-x">Compared to matched peers</a>, students who had been hospitalised with an injury had a 12% higher risk of not achieving the NMS in numeracy on NAPLAN and a 9% higher risk of not achieving the NMS in reading.</p>
<p><strong>Asthma</strong></p>
<p>Around <a href="https://www.aihw.gov.au/reports/children-youth/australias-children/contents/health/asthma-prevalence-children">460,000 young people</a> have asthma in Australia. If asthma is not adequately controlled, it can have a wide-ranging impact on their lives, including on their performance at school.</p>
<p>Our <a href="https://doi.org/10.1111/cea.14022">analysis</a> of 28,114 young people hospitalised with asthma showed a difference between the sexes. Young males’ risk of not achieving the NMS was 13% higher for numeracy and 15% higher for reading compared to matched peers. In contrast, females hospitalised with asthma showed no difference.</p>
<p><strong>Mental illness</strong></p>
<p>Around 14% of young people experience a mental illness in Australia that can affect their health, relationships and school life. In our <a href="https://doi.org/10.1177/00048674211061684">study</a> of 7,069 young people hospitalised with a mental illness, young males had almost twice the risk of not achieving the NMS on NAPLAN for both numeracy and reading compared to their peers. Young females had a 1.5 times higher risk of not achieving the NMS for numeracy and those with diagnosed <a href="https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/conduct-disorder">conduct disorder</a> had twice the risk of not achieving the NMS for reading.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/the-transition-into-adolescence-can-be-brutal-for-kids-mental-health-but-parents-can-help-reduce-the-risk-180487">The transition into adolescence can be brutal for kids' mental health – but parents can help reduce the risk</a>
</strong>
</em>
</p>
<hr>
<p><strong>Epilepsy</strong></p>
<p>Across the country, about <a href="https://epilepsyfoundation.org.au/about-us/media-room/#:%7E:text=1%20in%20200%20Australian%20children%20live%20with%20epilepsy.">one in 200 children</a> are living with epilepsy. Epilepsy can affect attention, concentration and memory, all which can be a barrier to performing well at school. </p>
<p>Our <a href="https://doi.org/10.1016/j.seizure.2022.05.014">study</a> of 2,383 young people hospitalised with epilepsy found young males and females had a three times higher risk of not achieving the NMS on NAPLAN for both numeracy and reading compared to peers.</p>
<p><strong>Type 1 diabetes</strong></p>
<p>Type 1 diabetes was the exception and showed no adverse impact on school performance. In Australia, an estimated 6,500 young people have type 1 diabetes. Our <a href="https://doi.org/10.1111/pedi.13317">analysis</a> of 833 young people hospitalised with type 1 diabetes did not find any difference in achieving the NMS in numeracy or reading on NAPLAN compared to matched peers.</p>
<p>This finding is likely explained by improved glucose control and type 1 diabetes management. It is also possible that school assessments, such as NAPLAN, do not capture everyday difficulties that students with diabetes experience.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/what-parents-can-do-to-make-a-childs-chronic-illness-easier-41359">What parents can do to make a child's chronic illness easier</a>
</strong>
</em>
</p>
<hr>
<h2>How can we support these students’ learning?</h2>
<p>It is essential that we identify students who are likely to need learning support because of an injury or chronic illness. Supports can include online learning options, flexible programming or mobilising peer support to enable sharing of class notes and homework activities. </p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1361455225442295808"}"></div></p>
<p>Monitoring students’ progress when they return to school will help to identify ongoing learning support needs.</p>
<p>There are also ways to manage symptoms and enhance performance at school. With asthma, for example, a comprehensive asthma management plan, using medication to manage symptoms, and <a href="https://www.schn.health.nsw.gov.au/find-a-service/health-medical-services/asthma-improvement">healthcare co-ordination</a> between GPs, hospitals and community services can all reduce the chance of ending up in hospital. For epilepsy, learning to identify seizure triggers, lifestyle and medication management are <a href="https://www.epilepsy.org.au/strong-foundations/overview/">key</a>.</p>
<p>Improving teachers’ understanding of symptom management for chronically ill or injured students is important too. For example, a New South Wales program, <a href="https://education.nsw.gov.au/early-childhood-education/whats-happening-in-the-early-childhood-education-sector/resource-library/asthma">Aiming for Asthma Improvement in Children</a>, encourages self-paced training for school staff on asthma management and first aid, along with resources for managing asthma in schools. For epilepsy, Strong Foundations provides <a href="https://www.epilepsy.org.au/strong-foundations/learning-and-participation/">advice</a> on the skills children with epilepsy need to manage in the classroom and playground.</p>
<p>Early identification and recognition that an injured or chronically ill student may need learning support at school and at home are critical to ensure they are not left behind academically.</p>
<hr>
<p><em>This article is part of The Conversation’s <a href="https://theconversation.com/topics/breaking-the-cycle-119149">Breaking the Cycle</a> series, which is supported by a philanthropic grant from the Paul Ramsay Foundation.</em></p><img src="https://counter.theconversation.com/content/184313/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Rebecca Mitchell has received funding from the NHMRC, the MRFF, the ARC, and various state and federal government departments for past projects. This research was funded by a philanthropic donor to Macquarie University. This article is part of The Conversation's Breaking the Cycle series, which is about escaping cycles of disadvantage. The series is supported by a philanthropic grant from the Paul Ramsay Foundation.</span></em></p><p class="fine-print"><em><span>Anne McMaugh has received funding from the Australian Research Council for past projects. This research was funded by a philanthropic donor to Macquarie University</span></em></p>A study of thousands of students hospitalised with an injury or illness confirms they are likely to fall behind their classmates. But good management and targeted help with learning cut the risk.Rebecca Mitchell, Associate Professor Health and Societal Outcomes, Macquarie UniversityAnne McMaugh, Senior Lecturer in Educational Psychology, Macquarie UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1774242022-04-20T12:16:04Z2022-04-20T12:16:04ZWhen it comes to the rarest of diseases, the diagnosis isn’t the answer – it’s just the starting point<figure><img src="https://images.theconversation.com/files/457534/original/file-20220411-23-x1ka5n.jpg?ixlib=rb-1.1.0&rect=0%2C10%2C3456%2C2223&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">The National Institutes of Health estimates the existence of 7,000 rare diseases, with some affecting only a handful of people.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/unaligned-dna-sequences-displayed-on-an-lcd-monitor-royalty-free-image/135899648?adppopup=true">Alan Phillips/E! via Getty Images</a></span></figcaption></figure><p>“Mr. and Mrs. Smith, we finally have an answer for you.” The couple, whose real names we are protecting for privacy, looked at me anxiously. I had been evaluating their young daughter, Sally, in <a href="https://www.cham.org/patients-families/find-a-doctor/melissa-p-wasserstein-md-1023066198">my role as a medical geneticist</a> at the Children’s Hospital at Montefiore in the Bronx, a borough of New York City. For years, the Smiths had been searching to learn why Sally was suffering from epilepsy, why she didn’t seem to understand them and why she wasn’t speaking at 6 years of age. In 2021, they ended up in my clinic.</p>
<p>I decided to send a sample of Sally’s blood for <a href="https://medlineplus.gov/genetics/understanding/testing/sequencing/">whole-exome sequencing</a>, a test that could identify a change in one of her genes that might be responsible for her symptoms. A few weeks later I had the answer. </p>
<p>“Sally has an extremely rare disorder that you’ve probably never heard of,” I told them. “It’s so rare that it doesn’t even have a real name yet. It’s called <a href="https://doi.org/10.1038/s12276-018-0098-x">NAA10-related disorder</a>.” The family looked at me with blank stares. I took a deep breath and continued. </p>
<p>The NAA10 gene codes for an enzyme that modifies critical proteins, enabling them to function properly. A single change in Sally’s NAA10 gene would cause the enzyme to be made incorrectly, resulting in intellectual disability and seizures. The NAA10 gene is located on the X chromosome, which is one of two sex chromosomes in humans. </p>
<p>Males typically carry an X and a Y chromosome, while females usually have two X chromosomes; as a result, boys are usually more severely affected and girls have a less predictable course. I explained to the family that only about 50 other people with NAA10-related disorder have been reported across the globe. They then asked me about treatment. I replied sadly, “none.” I could see them struggling to wrap their heads around this. </p>
<p>They asked further questions about what might happen to Sally: Will she learn to speak? Will she be able to learn? Will she grow old? I told them that there is not enough experience to accurately predict what Sally’s future will look like. Feeling useless, I said, “Here is a patient support group that might be helpful.” And with nothing more to offer, I added: “I’ll see you in a year.”</p>
<p>Moments like this – a long-awaited answer that is met with more bewilderment than relief – are not uncommon in the practice of medical genetics. Most people expect that after a long, frustrating search, finding the underlying diagnosis will provide answers and a path forward. But sometimes, in cases like Sally’s, the answer simply begets more questions.</p>
<p>We’ve faced these difficult questions as two researchers with decades of experience in rare genetic diseases. One of us is a <a href="https://www.cham.org/patients-families/find-a-doctor/melissa-p-wasserstein-md-1023066198">medical geneticist</a> whose clinical work focuses on the diagnosis and management of individuals with rare genetic disorders; the <a href="https://www.einsteinmed.edu/faculty/7668/steven-walkley/">other is a neuroscientist</a> working to determine how rare genetic diseases impact brain function and possible ways to correct them. </p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/7QKum6ihGyE?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">They are called “rare diseases,” but approximately 350 million people worldwide are living with one.</span></figcaption>
</figure>
<h2>Putting ‘rare’ disease into context</h2>
<p>Most so-called rare diseases are poorly understood and have no treatment. The National Institutes of Health has estimated that there are about 7,000 rare diseases, defined as ones affecting <a href="https://rarediseases.info.nih.gov/diseases/pages/31/faqs-about-rare-diseases#">fewer than 200,000 Americans</a>. Many rare diseases, however, are like NAA10-related disorders and affect only a handful of individuals.</p>
<p>Major advances in the <a href="https://theconversation.com/record-breaking-rapid-dna-sequencing-promises-timely-diagnosis-for-thousands-of-rare-disease-cases-175480">precision and speed of gene sequencing technology</a> – followed by dramatic reductions in the costs of testing – have radically changed how medical genetics clinics function. Next-generation genetic sequencing, which was so expensive just a decade ago that it was used only after all other testing options had been exhausted, is now the go-to test in most clinics. </p>
<p>But while sequencing can provide confirmation of a suspected, well-understood condition, it frequently results in a situation like that faced by the Smiths, where the testing result shows an incredibly rare disorder with little known about it. </p>
<h2>Putting the puzzle pieces together</h2>
<p>The speed and ease with which modern gene sequencing can generate a diagnosis stand in sharp contrast to the prolonged effort required to understand how the genetic variant causes disease. Humans all <a href="https://medlineplus.gov/genetics/understanding/basics/gene/#">have the same 20,000-plus genes</a>, which govern the traits that make us characteristically human, such as a large brain, 10 fingers and round pupils. Changes, or variants, in these genes <a href="https://medlineplus.gov/genetics/understanding/mutationsanddisorders/genemutation">determine our uniqueness</a>. So while we all have genes that tell our bodies to make hair, variants in these genes can make hair that is straight or curly, brown or red. Some genetic variants, however, change the gene product so significantly that they result in disease. </p>
<p>Unraveling the natural history of a rare condition requires years of focused attention by clinicians and scientists. Researchers like us also work to piece together the complex puzzle of how a rare genetic difference can alter metabolic pathways in the brain, as well as other organs that might be affected. </p>
<p>Over time, a fuller picture of the rare disorder begins to emerge. The role of the gene in normal cells or commoner diseases unfolds, as well as possible therapies. For instance, potential treatments might involve <a href="https://doi.org/10.1016/S0140-6736(22)00057-5">replacing or modifying a gene</a> that isn’t properly functioning, <a href="https://doi.org/10.1182/blood.V78.5.1183.1183">infusing a vital enzyme</a> that an individual’s body isn’t making or prescribing a specialized diet or medications. But before one can determine how to treat a genetic disease, researchers first need to determine what is altered and not working normally. Only after this is understood can we begin to envision treatment.</p>
<h2>Personalized medicine offers a way forward</h2>
<p>To provide our patients and their families with more answers, we here at the Albert Einstein College of Medicine <a href="https://einsteinmed.edu/centers/iddrc/">have begun a program</a> in which we build what we call Gene Teams. These consist of parents or caregivers, their child’s physician and interested scientists and their trainees. These researchers are typically working on deciphering the gene’s function, its encoded protein or the role the gene or protein plays inside of cells. </p>
<p>We bring all the team members together, and the child’s physician outlines what is known about the clinical condition, followed by the parents sharing their child’s story. The scientists and their trainees then provide an accessible tutorial to the families about what the gene and its associated protein do in cells. Whenever possible our team also discusses ways by which the condition could be treated. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/458451/original/file-20220418-12-qaf49e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Two families, each of whom has a child with a rare genetic disease, stand facing one another and smiling." src="https://images.theconversation.com/files/458451/original/file-20220418-12-qaf49e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/458451/original/file-20220418-12-qaf49e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=562&fit=crop&dpr=1 600w, https://images.theconversation.com/files/458451/original/file-20220418-12-qaf49e.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=562&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/458451/original/file-20220418-12-qaf49e.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=562&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/458451/original/file-20220418-12-qaf49e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=707&fit=crop&dpr=1 754w, https://images.theconversation.com/files/458451/original/file-20220418-12-qaf49e.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=707&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/458451/original/file-20220418-12-qaf49e.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=707&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Two families - the Foglio family on the left and the Robl family on the right – meet at the Albert Einstein College of Medicine on Rare Disease Day 2020 to exchange experiences on building rare disease foundations. The Foglios, who have a son with a rare variant in the SLC17A5 gene, created the STAR Foundation. The Robl family created the KARES Foundation following one of their daughters’s diagnosis with a rare mutation in the KDM5C gene.</span>
<span class="attribution"><span class="source">Albert Einstein College of Medicine</span></span>
</figcaption>
</figure>
<p>These tutorials are the first encounters in ongoing relationships. Remarkably, three different families who were empowered by their Gene Team experience have gone on to establish foundations focused on their child’s disease, and they have built networks to other families affected by the same rare condition worldwide. These are the <a href="https://www.sallaresearch.org">STAR Foundation</a> for SLC17A5, the <a href="https://www.kdm5cfoundation.org/home">KARES Foundation for KDM5C</a> and the <a href="https://www.cacna1a.org/">CACNA1A Foundation</a>. The scientists, too, after the team meetings, have often gone on to build major research projects, some focused on the exact variant observed in the affected child. </p>
<p>[<em>Over 150,000 readers rely on The Conversation’s newsletters to understand the world.</em> <a href="https://memberservices.theconversation.com/newsletters/?source=inline-150ksignup">Sign up today</a>.]</p>
<p>We as scientists and our trainees have also been transformed by our involvement with the Gene Teams. Working directly with the families brings real-life experience to our laboratory work and inspires us and other researchers to remember that our work matters – not only for expanding scientific knowledge but also for helping families in need. </p>
<p>We have learned that the blank stare experienced in the doctor’s office following diagnosis of a rare disease can be transformed by empowering families not only with greater knowledge of the involved gene, but also with an understanding that they are not alone and that there can be a more hopeful path forward.</p><img src="https://counter.theconversation.com/content/177424/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Steven Walkley receives funding from the National Institutes of Health. </span></em></p><p class="fine-print"><em><span>Melissa Wasserstein receives funding from the National Institutes of Health</span></em></p>Deciphering the biological pathways behind rare genetic diseases often involves assembling a team of specialists to work closely with the family members of those affected.Steven Walkley, Professor of Neuroscience, Pathology and Neurology, Albert Einstein College of MedicineMelissa Wasserstein, Professor of Pediatric Genetic Medicine, Albert Einstein College of MedicineLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1722802022-02-01T13:14:03Z2022-02-01T13:14:03ZSeizures can cause memory loss, and brain-mapping research suggests one reason why<figure><img src="https://images.theconversation.com/files/443023/original/file-20220127-4399-lt0flk.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C1732%2C1732&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">In addition to memory loss, seizures can result in a complete loss of consciousness.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/digital-artwork-of-human-mental-energy-royalty-free-illustration/1283557418">pressureUA/iStock via Getty Images Plus</a></span></figcaption></figure><p><a href="https://doi.org/10.1016/j.eplepsyres.2017.11.015">Epilepsy</a> is a disease marked by recurrent seizures, or sudden periods of abnormal, excessive or synchronous neuronal activity in the brain. <a href="https://www.epilepsy.com/make-difference/public-awareness/1-26#">One in 26 people</a> in the U.S. will develop epilepsy at some point in their life. While people with mild seizures might experience a brief loss of awareness and muscle twitches, more severe seizures could last for several minutes and lead to injury from falling down and losing control of their limbs. </p>
<p>Many people with epilepsy also experience memory problems. Patients often experience retrograde amnesia, where they cannot remember what happened immediately before their seizure. Electroconvulsive therapy, a form of treatment for major depression that intentionally triggers small seizures, can also <a href="https://doi.org/10.1016/j.jad.2011.02.026">cause retrograde amnesia</a>. </p>
<p>So why do seizures often cause memory loss?</p>
<p>We are <a href="https://scholar.google.com/citations?user=bjrXv58AAAAJ&hl=en&oi=ao">neurology</a> <a href="https://scholar.google.com/citations?user=nMb-pTcAAAAJ&hl=en">researchers</a> who study the mechanisms behind how seizures affect the brain. Our <a href="https://doi.org/10.1016/j.pneurobio.2020.101984">brain-mapping study</a> found that seizures affect the same circuits of the brain responsible for memory formation.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/LcO9YU-Pdws?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">One of the earliest descriptions of seizures was written on a Babylonian tablet over 3,000 years ago.</span></figcaption>
</figure>
<h2>Why do seizures cause memory loss?</h2>
<p>Seizures can be caused by a number of factors, ranging from <a href="https://www.epilepsy.com/learn/epilepsy-due-specific-causes/structural-causes-epilepsy">abnormalities in brain structure</a> and <a href="https://www.epilepsy.com/learn/epilepsy-due-specific-causes/genetic-causes-epilepsy">genetic mutations</a> to <a href="http://scitechconnect.elsevier.com/connections-between-infections-seizures">infections</a> and <a href="https://rarediseases.info.nih.gov/diseases/11979/autoimmune-encephalitis">autoimmune conditions</a>. Often, the root cause of a seizure <a href="https://dx.doi.org/10.4103%2Fjfmpc.jfmpc_322_16">isn’t known</a>.</p>
<p>The most common type of epilepsy involves seizures that originate in the brain region located behind the ears, the <a href="https://emedicine.medscape.com/article/1184509-overview">temporal lobe</a>. Some patients with temporal lobe epilepsy experience retrograde amnesia and are unable to recall events immediately before their seizure. </p>
<p>This may be because these seizures affect the <a href="https://doi.org/10.1016/0301-0082(91)90011-O">hippocampus</a>, a region in the temporal lobe important for memory storage and processing. During sleep, the hippocampus transmits new information learned during the day to another part of the brain called the cerebral cortex in order to consolidate it into new memories. This process occurs through many brain pathways connecting the hippocampus to the cortex. </p>
<p>With this in mind, our research group wondered if the electrical signals of seizures might also follow the same routes the brain uses for memory consolidation instead of creating their own separate path. We reasoned that disruption of this pathway might cause memory loss.</p>
<p>To figure this out, we trained mice to navigate a T-shaped maze to find a reward of sweetened condensed milk. The mice had to learn how to alternate between the left and the right arm of maze in a specific pattern to be given milk. When the mice were able to obtain the milk 80% of the time, we determined that the mice had successfully consolidated their memory of how to navigate the maze.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/cL7H5Sxw1KM?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">T mazes are used to assess spatial learning and memory.</span></figcaption>
</figure>
<p>Fifteen minutes after the mice successfully learned how to navigate the maze, we injected them with a drug that causes seizures. The day following the seizure, we found that the mice performed poorly on the maze, as though they hadn’t learned how to navigate it in the first place. This confirmed that a single seizure was enough for the mice to forget what they learned just before the seizure. </p>
<p>Our next step was to figure out why seizures caused the mice to forget what they learned. To identify which parts of the brain were active during the learning process and during seizures, we used genetically engineered mice whose neurons produce a red protein when activated. We mapped the neurons of these mice as they were learning how to navigate the maze and during the induced seizures. In analyzing these maps, we found that learning and seizures activated the same brain circuits in the hippocampus and cortex. Because they use the same brain pathways, seizures can disrupt the memory consolidation process by taking over the circuit. This meant that seizures can hijack the memory pathways and cause amnesia.</p>
<p>Because memory is networked throughout the brain, memory impairments might not necessarily stem just from interference in the hippocampus alone. Future studies on other brain regions will further clarify how seizures cause memory loss.</p>
<p>[<em>Understand new developments in science, health and technology, each week.</em> <a href="https://memberservices.theconversation.com/newsletters/?nl=science&source=inline-science-understand">Subscribe to The Conversation’s science newsletter</a>.]</p><img src="https://counter.theconversation.com/content/172280/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jaideep Kapur receives funding from the NIH and the University of Virginia. He is the chair of the International League against Epilepsy North America, a member of the Board of Directors of the American Epilepsy Society, and a member of the Scientific Advisory Committee of the CURE Epilepsy Foundation.</span></em></p><p class="fine-print"><em><span>Anastasia Brodovskaya does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Many people with epilepsy are unable to remember what happened immediately before they have a seizure. This may be because seizures and memory use the same pathways of the brain.Anastasia Brodovskaya, Postdoctoral Fellow in Neurology, University of VirginiaJaideep Kapur, Professor of Neuroscience and Neurology, University of VirginiaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1721452021-12-29T21:26:56Z2021-12-29T21:26:56Z5 things research from twins taught us about health, behaviour and what makes us unique<figure><img src="https://images.theconversation.com/files/436555/original/file-20211209-140109-1g6swwj.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://unsplash.com/photos/M-adWhDQd7Y">Keisha Montfleury/Unsplash</a></span></figcaption></figure><p>Researchers often compare the differences between identical and fraternal twins to better understand health and behaviour. </p>
<p>The first major insight is that genes and environments almost always combine to influence our life trajectory. Sometimes the largest factor is genetics (think genetic disorders). Sometimes it’s environment (think infections). Mostly, it’s somewhere in between. </p>
<p>Such studies have accelerated the search for genes and environmental agents that cause or trigger diseases. This has helped us understand, treat and even prevent diseases. As twin research has <a href="https://www.twins.org.au/research/tools-and-resources/125-conversation-in-twin-research/377-twin-research-designs-and-analytic-approaches">matured</a>, it has progressed to addressing important questions about when and how diseases originate. </p>
<p>So what has research from twins taught us about specific diseases and the human body?</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/seeing-double-why-twins-are-so-important-for-health-and-medical-research-5273">Seeing double: why twins are so important for health and medical research</a>
</strong>
</em>
</p>
<hr>
<h2>1. Smoking increases the risk of bone fracture</h2>
<p>Most studies linking environment and disease are complicated by genetic factors. To get around this, we can work with twins who differ in environmental factors. </p>
<p>One such <a href="https://www.nejm.org/doi/full/10.1056/nejm199402103300603">Australian study from 1994</a> compared 20 pairs of female twins in which only one of each pair was a long-term, heavy smoker. </p>
<p>The researchers found smoking one pack of cigarettes a day for 20 years resulted in sufficient loss in bone density to cause osteoporosis. This doubled the risk of having a bone fracture. </p>
<p>This provided compelling evidence that smoking causes osteoporosis and an increased risk of bone fractures.</p>
<h2>2. Events around the time of birth are not a major cause of epilepsy</h2>
<p>Epilepsy is a group of disorders where brain activity is abnormal and seizures are the presenting feature. Traditionally, diagnosis was not possible until after a person’s first seizure, which can occur at any stage of life, from babies to the elderly.</p>
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4166361/">Twin studies</a> since the 1960s have shown a mix of genes and environment cause epilepsy. However, until the early 1990s, it was assumed that problems during the birthing process were a major cause of epilepsy.</p>
<figure class="align-center ">
<img alt="Older men stand beside each other, smiling." src="https://images.theconversation.com/files/436563/original/file-20211209-68670-15wadz1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/436563/original/file-20211209-68670-15wadz1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/436563/original/file-20211209-68670-15wadz1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/436563/original/file-20211209-68670-15wadz1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/436563/original/file-20211209-68670-15wadz1.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/436563/original/file-20211209-68670-15wadz1.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/436563/original/file-20211209-68670-15wadz1.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Identical twins share almost all their DNA.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/senior-twin-men-smiling-on-camera-1919843804">Shutterstock</a></span>
</figcaption>
</figure>
<p>Obstetricians and midwives were often blamed for causing epilepsy. However, a <a href="https://pubmed.ncbi.nlm.nih.gov/8255449/">twin study</a> in 1993 did not support a link between minor problems during birth and the later development of epilepsy. </p>
<p>This information has helped doctors and their patients better understand the causes of epilepsy and not necessarily attribute blame to the birthing process.</p>
<h2>3. Identical twins are different under the skin from before birth</h2>
<p>Genetically identical twins nearly always look identical. Yet, at birth, they have already accumulated differences in the structure and function of their genes. </p>
<p>These <a href="https://press.princeton.edu/books/hardcover/9780691173887/innate">differences</a> are caused by a mix of chance events and individual experiences in the womb.</p>
<p>The location a fertilised egg implants in the womb is random, but some locations are more favourable to growth. For the subset of identical twins who split before they reach the womb, different locations could create different environments in which a baby develops. </p>
<figure class="align-center ">
<img alt="Twin newborn babies sleep, their arms raised." src="https://images.theconversation.com/files/436558/original/file-20211209-142574-qu4qd5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/436558/original/file-20211209-142574-qu4qd5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=305&fit=crop&dpr=1 600w, https://images.theconversation.com/files/436558/original/file-20211209-142574-qu4qd5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=305&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/436558/original/file-20211209-142574-qu4qd5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=305&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/436558/original/file-20211209-142574-qu4qd5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=384&fit=crop&dpr=1 754w, https://images.theconversation.com/files/436558/original/file-20211209-142574-qu4qd5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=384&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/436558/original/file-20211209-142574-qu4qd5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=384&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Identical, but still different.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/sleeping-newborn-identical-boy-twins-267663011">Shutterstock</a></span>
</figcaption>
</figure>
<p>As a result of this or other chance events, around one in six twins differ more than 20% in weight at birth, which may be associated with an increased <a href="https://obgyn.onlinelibrary.wiley.com/doi/10.1111/aogs.13613">risk</a> of illness at birth, especially for the smaller twin. </p>
<p>Such individual experiences could also help explain Brazilian twin pairs in which only one child was born with <a href="https://www.mdpi.com/2414-6366/5/4/188">Zika virus</a> infection.</p>
<h2>4. Leukaemia originates before birth</h2>
<p>Changes in the genetic sequence of blood cells can predispose people to develop leukaemia (cancer of the blood). </p>
<p>Such changes are unique to each person but <em>when</em> these changes happened to people used to be a mystery. That was until identical twin children were <a href="https://www.sciencedirect.com/science/article/pii/S0006497120768072?via%3Dihub">discovered with leukaemias</a> originating from the same cell. </p>
<p>Lymphocytes (white blood cells) of the immune system shuffle their immune genes at random, making each person genetically unique, even identical twins. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/same-same-but-different-when-identical-twins-are-non-identical-112684">Same same but different: when identical twins are non-identical</a>
</strong>
</em>
</p>
<hr>
<p>The researchers <a href="https://www.sciencedirect.com/science/article/pii/S0006497120768072?via%3Dihub">concluded</a> the leukaemia started in one twin in the womb and spread to the other twin through blood vessels in a shared placenta. </p>
<p>But while the first step towards leukaemia happened before birth, the cancer progression differed among the twins, resulting in leukaemia being diagnosed at different ages.</p>
<p>This provided the first evidence that some leukaemias can lay dormant for years and enabled future research that would pinpoint the events along this process. </p>
<h2>5. Many twins don’t know if they’re identical or fraternal</h2>
<p>Identical twins start as one fertilised egg that splits after a few days. They share almost 100% of their DNA and are almost always the same sex. </p>
<p>Fraternal twins result from two eggs fertilised around the same time. They’re as genetically different as any pair of siblings and can have the same, or different sex. </p>
<figure class="align-center ">
<img alt="Twin women hug outside in the sunshine." src="https://images.theconversation.com/files/437106/original/file-20211213-25-1fbing6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/437106/original/file-20211213-25-1fbing6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/437106/original/file-20211213-25-1fbing6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/437106/original/file-20211213-25-1fbing6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/437106/original/file-20211213-25-1fbing6.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/437106/original/file-20211213-25-1fbing6.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/437106/original/file-20211213-25-1fbing6.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Fraternal twins are as genetically different as a pair of siblings.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/portrait-identical-ginger-twin-sisters-smiling-723502963">Shutterstock</a></span>
</figcaption>
</figure>
<p>In 2012, my colleagues and I at <a href="https://www.twins.org.au/">Twins Research Australia</a> conducted a study at a national twins festival on pairs who had any uncertainty about their genetic identity. We used “genetic fingerprinting” on DNA from cheek swabs provided by same-sex twins of all ages. This test is the definitive way of discovering whether twins are identical or fraternal. </p>
<p>We compared this with perceptions of the twins themselves before they took the test. </p>
<p>We <a href="https://www.twins.org.au/research/tools-and-resources/125-conversation-in-twin-research/374-the-importance-of-zygosity-knowledge-for-twins-and-science">found</a> almost one-third of the twins we tested had been either incorrect or unsure about their genetic identity. Some had even been misinformed by medical professionals. </p>
<p>The universal sentiment was twins and their families felt better knowing the truth. Our data enabled us to develop better educational <a href="https://www.twins.org.au/twins-and-families/expecting-twins">resources</a> for twins and their advocates to know more about themselves. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/not-all-twins-are-identical-and-thats-been-an-evolutionary-puzzle-until-now-138209">Not all twins are identical and that's been an evolutionary puzzle, until now</a>
</strong>
</em>
</p>
<hr>
<img src="https://counter.theconversation.com/content/172145/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jeffrey Craig is Deputy Director of Twins Research Australia and President of the International Society for Twin Studies. He receives funding from the IMPACT Institute, Deakin University, the National Health and Medical Research Council, Australia, and the Waterloo Foundation, UK. He is affiliated with the Gene(e)quality Network. </span></em></p>Genes and environments almost always combine to influence our risk of diseases. Research in twins has helped us understand how.Jeffrey Craig, Professor in Medical Sciences, Deakin UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1681682021-12-14T13:26:48Z2021-12-14T13:26:48ZBlocking an immune system molecule in mice may help prevent long-term disabilities after traumatic brain injury<figure><img src="https://images.theconversation.com/files/436207/original/file-20211207-141213-17pbntd.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C2090%2C1432&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">An estimated 69 million people worldwide experience a traumatic brain injury every year.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/mri-brain-with-headache-royalty-free-image/938046810">Iaremenko/iStock via Getty Images Plus</a></span></figcaption></figure><p><em>The <a href="https://theconversation.com/us/topics/research-brief-83231">Research Brief</a> is a short take about interesting academic work.</em></p>
<h2>The big idea</h2>
<p>Blocking an immune system molecule that accumulates after traumatic brain injury could significantly reduce the injury’s detrimental effects, according to a recent mouse study <a href="https://gladstone.org/people/jeanne-paz">my neuroscience lab and I</a> published <a href="https://doi.org/10.1126/science.abj2685">in the journal Science</a>.</p>
<p>The <a href="https://courses.lumenlearning.com/teachereducationx92x1/chapter/cerebral-cortex/">cerebral cortex</a>, the part of the brain involved in thinking, memory and language, is often the primary site of head injury because it sits directly beneath the skull. However, we found that another region near the center of the brain that regulates sleep and attention, the <a href="https://doi.org/10.1016/j.neuron.2019.06.005">thalamus</a>, was even more damaged than the cortex months after the injury.</p>
<p>This may be due to increased levels of a molecule called C1q, which triggers a part of the immune system called the <a href="https://doi.org/10.1186/s12974-020-02024-8">classical complement pathway</a>. This pathway plays a key role in rapidly clearing pathogens and dead cells from the body and helps control the inflammatory immune response.</p>
<figure>
<iframe width="440" height="260" src="https://www.youtube.com/embed/BSypUV6QUNw?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">A branch of the immune system called the complement system is composed of trillions of proteins that enhance immune response.</span></figcaption>
</figure>
<p>C1q plays both <a href="https://doi.org/10.1186/s12974-020-02024-8">helpful and harmful roles in the brain</a>. On the one hand, accumulation of C1q in the brain can trigger abnormal elimination of synapses – the structures that allow neurons to communicate with one another – and <a href="https://doi.org/10.1126/science.aad8373">contribute to neurodegenerative disease</a>. On the other hand, C1q is also involved in <a href="https://doi.org/10.1016/j.cell.2007.10.036">normal brain development</a> and <a href="https://doi.org/10.1186/s12974-018-1066-z">protects the central nervous system from infection</a>. </p>
<p>In the case of traumatic brain injury, we found that C1q lingered in the thalamus at abnormally high levels for months after the initial injury and was associated with inflammation, dysfunctional brain circuits and neuronal death. This suggests that higher levels of C1q in the thalamus could contribute to several long-term effects of traumatic brain injury, such as sleep disruption and epilepsy.</p>
<p>C1q does provide some protection for the brain during traumatic injury, however. When we used genetically engineered mice that lack C1q at the time of trauma, the brain injury appeared much worse. This suggests that C1q is likely very important right when the injury happens in preventing cell death.</p>
<p>We collaborated with scientists at the biopharmaceutical company Annexon Biosciences to see if we could avoid C1q’s detrimental effects without losing its protective ones. We found that treating mice with an antibody that blocks C1q 24 hours after brain injury prevented detrimental effects like chronic inflammation and neuronal loss in the thalamus. Additionally, antibody treatment helped restore disrupted <a href="https://doi.org/10.1016/j.cub.2018.03.046">sleep spindles</a> – these are normal brain rhythms during the early stages of sleep that are important for memory consolidation. It also prevented the development of <a href="https://www.ncbi.nlm.nih.gov/books/NBK98139/">epileptic spikes</a>, or abnormal fluctuations in brain activity, which can disrupt <a href="https://doi.org/10.1016/0013-4694(88)90004-1">cognition and behavior</a>.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/436214/original/file-20211207-19-julmtx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Illustration of IgM bound to antigens on the surface of a membrane and activating the C1 complex of the complement system." src="https://images.theconversation.com/files/436214/original/file-20211207-19-julmtx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/436214/original/file-20211207-19-julmtx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/436214/original/file-20211207-19-julmtx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/436214/original/file-20211207-19-julmtx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/436214/original/file-20211207-19-julmtx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=565&fit=crop&dpr=1 754w, https://images.theconversation.com/files/436214/original/file-20211207-19-julmtx.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=565&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/436214/original/file-20211207-19-julmtx.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=565&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">C1q is part of a larger structure called C1, colored here in violet. When activated, this C1 structure plays a role in attracting and activating immune cells to attack invaders and clear foreign and damaged debris.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/igm-mediated-complex-activation-molecular-model-royalty-free-image/1316978215">Juan Gaertner/Science Photo Library via Getty Images</a></span>
</figcaption>
</figure>
<h2>Why it matters</h2>
<p>Traumatic brain injury can happen to anyone. It affects <a href="https://doi.org/10.3171/2017.10.jns17352">69 million people worldwide per year</a> and is a <a href="https://www.who.int/mental_health/neurology/neurological_disorders_report_web.pdf">leading cause of disability</a> in children and adults. Yet there are currently no therapies available to prevent the long-term disabilities that can result from brain trauma, such as epilepsy, sleep disruption and sensory processing difficulty.</p>
<p>We believe that targeting C1q after a brain injury could have protective benefits and help prevent some of the devastating consequences. Our study also answered some big questions in the field about where and how changes happen in the brain after trauma, and which ones actually cause deficits.</p>
<h2>What still isn’t known</h2>
<p>It remains unknown whether blocking C1q could also prevent epileptic seizures that develop after severe traumatic brain injury. Researchers <a href="https://doi.org/10.1038/s41582-021-00461-4">are looking for biomarkers</a> that would help identify people at high risk of developing epilepsy and working to understand the basic mechanisms leading from <a href="https://doi.org/10.1007/s13311-021-01119-1">traumatic brain injury to epilepsy</a>. There is no cure yet for post-traumatic epilepsy.</p>
<h2>What’s next</h2>
<p>My lab will continue working to expand our understanding of what happens in the brain after injury. Next, we want to focus on whether we can target C1q to prevent the convulsive seizures often reported among people with severe traumatic brain injuries.</p>
<p>C1q inhibitors are currently being tested in clinical trials for an autoimmune disorder known as <a href="https://n.neurology.org/content/94/15_Supplement/763">Guillain-Barré syndrome</a>. This could help accelerate treatment development for patients with traumatic brain injury.</p><img src="https://counter.theconversation.com/content/168168/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jeanne Paz receives funding from the Department of Defense and the NIH. This research was conducted collaboratively with Annexon Biosciences.</span></em></p>The molecule C1q has both protective and detrimental effects after traumatic brain injury. Blocking it after injury in mice restored normal brain rhythms during sleep and prevented epileptic spikes.Jeanne Paz, Associate Investigator at Gladstone Institutes and Associate Professor of Neurology, University of California, San FranciscoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1662022021-08-31T15:09:50Z2021-08-31T15:09:50ZA plant grown in Nigeria shows potential for epilepsy treatment<figure><img src="https://images.theconversation.com/files/418447/original/file-20210830-29-11ezvzx.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A plant fruit in Nigeria shows potential for a new drug for epilepsy treatment. </span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/illustration/brain-and-brain-waves-in-epilepsy-royalty-free-illustration/956351642?adppopup=true">Kateryn Kon/Science Photo Library</a></span></figcaption></figure><p><a href="https://www.who.int/news-room/fact-sheets/detail/epilepsy">Epilepsy</a> is a brain disorder that arises from imbalances of brain chemicals called neurotransmitters. This disorder manifests as recurring seizure, unconsciousness and momentary loss of memory. These events are frequent and unpredictable. This is because the brain cells called neurons either overwork or are unable to balance the release of two chemicals that are vital for normal brain function: gamma aminobutyric acid and glutamate. </p>
<p>The burden of epilepsy in Nigeria is high, with <a href="https://pubmed.ncbi.nlm.nih.gov/30690324/">estimated prevalence</a> of eight per 1,000 people. </p>
<p>Adults over 55 years of age <a href="https://www.epilepsybehavior.com/article/S1525-5050(18)30942-9/fulltext">have a higher risk</a> factor of developing epilepsy because they are more likely to have head injury, stroke or develop brain tumours or Alzheimer’s disease, which can all cause epilepsy. But epilepsy does occur in childhood too.</p>
<p>Epilepsy is a serious condition and it can be difficult to find the right drug to treat it. Some commonly used antiepileptic drugs may show <a href="https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(12)70153-9/fulltext">adverse effects</a>. Most are expensive, and some may be ineffective. There’s therefore a need to explore new alternatives. </p>
<p>A plant that grows in Nigeria shows promise as the source of a new drug.</p>
<p><em>Tetrapleura tetraptera</em> also known as aidan and uyayak, is a tree found in the <a href="https://face2faceafrica.com/article/five-amazing-health-benefits-of-aidan-fruits-you-probably-didnt-know">West African</a> rainforest belt. It is single-stemmed and about 30 m in height. Its fruit, the most utilised part, is green when unripe, dark red-brown when fully ripe, and 22-27 cm in length. This fruit gives a characteristic aromatic odour, making it a sought-after spice in some Nigerian dishes. </p>
<p>Some traditional medical practices, as well as <a href="https://onlinelibrary.wiley.com/doi/10.1002/ptr.1779">research reports</a>, piqued our interest in its potential in epilepsy management.</p>
<p>Our <a href="http://www.neurosciencenigeria.org/wp-content/uploads/2021/04/NJN_10.47081_njn2021.12.1_004.pdf">research</a> into the plant found that an extract of its fruit could protect against seizure and prevent brain degeneration. It could therefore be studied further for the development of a new antiepileptic drug.</p>
<h2>What we did</h2>
<p>To test the plant’s properties, we induced sustained seizure in laboratory animals and gave the fruit extract to some of the animals. We gave a standard antiepileptic drug, sodium valproate, to another group of animals. </p>
<p>Approval for the study was granted by the Faculty of Basic Medical Sciences Ethical Committee, University of Uyo, Nigeria. All <a href="https://www.ncbi.nlm.nih.gov/books/NBK54050/">recommendations and protocols</a> involving handling and care of the animals by the National Research Council of the United States of America were strictly adhered to in our research. </p>
<p>The aidan extract prevented the manifestation of seizure just like the sodium valproate.</p>
<p>Epilepsy causes <a href="https://link.springer.com/chapter/10.1007%2F978-3-319-57193-5_12">brain cell degeneration</a>. But we found that aidan protected the animals’ brains against degeneration better than the sodium valproate.</p>
<p>Neurodegenerative diseases <a href="https://www.healthline.com/health/brain-disorders#types">cause</a> the brain and nerves to deteriorate over time. They can change personality and cause confusion. They can also destroy brain tissue and nerves.</p>
<p>We found useful properties in the plant’s phytochemicals – the compounds it produces. Phytochemicals, also called <a href="https://www.intechopen.com/chapters/62876">secondary metabolites</a>, are the active constituents of such plants. These include tannins, phenolics, saponins, alkaloids, steroids, flavonoids and terpenoids. Metabolites help the body to withstand stress, overcome cell injury and fight against germs, among other functions. </p>
<p>The ratios of these phytochemicals to one another determine the unique properties of plants. Aidan is rich in phenols, alkaloids and flavonoids; these phytochemicals are responsible for the <a href="https://nutritionj.biomedcentral.com/articles/10.1186/s12937-016-0186-5">antioxidant</a> properties of plants known to protect against metabolic <a href="https://www.frontiersin.org/articles/10.3389/fphar.2018.01162/full">stress</a>. Metabolic stress often leads to a spectrum of disease conditions. </p>
<p>Aidan is also a <a href="https://www.hindawi.com/journals/jchem/2020/1608341/">source</a> of calcium, phosphorous, potassium, zinc and vitamins. This makes the plant very useful nutritionally and <a href="https://www.sciencedirect.com/science/article/abs/pii/S0378874104003137?via%3Dihub">medicinally</a>. </p>
<h2>What next?</h2>
<p>Our findings are important as the potentials of this plant can be explored for antiepileptic drug development. As a natural product, it does not only possess antiepileptic activity, it has numerous constituents that may also serve as alternative medication or an addition to medications in other related disease conditions.</p>
<p>Clinical trials of either crude or pure samples can be undertaken for anti-epileptic drug development as a first phase of clinical utilisation of the plant.</p><img src="https://counter.theconversation.com/content/166202/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Moses B. Ekong does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>An extract of a plant’s fruit in Nigeria could protect against seizure and prevent brain degeneration. It could therefore be studied further for the development of a new antiepileptic drug.Moses B. Ekong, Senior Lecturer, University of UyoLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1496122020-11-17T20:00:02Z2020-11-17T20:00:02ZCBD sales are soaring, but evidence is still slim that the cannabis derivative makes a difference for anxiety or pain<figure><img src="https://images.theconversation.com/files/369455/original/file-20201115-13-1k9f1pk.jpg?ixlib=rb-1.1.0&rect=0%2C43%2C4792%2C2953&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Hundreds of CBD products – including gummies – are now on the market.</span> <span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/gummies-from-medical-mary-are-on-display-at-the-6th-annual-news-photo/1171381576?adppopup=true">Frederic J. Brown via Getty Images</a></span></figcaption></figure><p>Many people have turned to <a href="https://doi.org/10.1080/10550887.2020.1811455">cannabis</a> and its derivatives as they search for pandemic relief, and one of the most widely available ones is CBD. It is also legal. You can buy oils, tinctures, capsules, gummies, cosmetics and even <a href="https://nordicbotanics.com/product/cbd-toilet-paper/">toilet paper</a> said to contain the molecule. <a href="https://www.marthastewart.com/7985856/martha-stewart-canopy-growth-cbd">Martha Stewart has a line of CBD products</a>, and some companies are marketing CBD products for holiday gifts. And, you can even buy CBD products for your pet.</p>
<p>An investment bank has estimated that this <a href="https://www.nytimes.com/2020/05/23/sunday-review/coronavirus-cbd-oil.html">market will be worth US$16 billion by 2025</a>, even though many of the products that allegedly contain CBD may <a href="https://www.fda.gov/news-events/public-health-focus/warning-letters-and-test-results-cannabidiol-related-products">not contain any CBD all</a>. And, if they do, the amount often is far less than the amount stated on the product bottle or box.</p>
<p>The CBD craze started in 2018, after the U.S. Food and Drug Administration <a href="https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-comprised-active-ingredient-derived-marijuana-treat-rare-severe-forms">approved</a> Epidiolex, the first drug containing CBD, used to treat two rare and severe types of childhood epilepsy. Since that approval, research on the possible medical applications of CBD has risen sharply.</p>
<p>But while the ads boasting its benefits are ubiquitous, there is still much we scientists don’t know, including <a href="https://theconversation.com/no-cbd-is-not-a-miracle-molecule-that-can-cure-coronavirus-just-as-it-wont-cure-many-other-maladies-its-proponents-claim-132492">whether CBD can actually reduce stress and anxiety</a>. </p>
<p>That said, <a href="https://scholar.google.com/citations?user=S9ykvZUAAAAJ&hl=en">as a neuroscientist</a> who studies childhood anxiety disorders and the neurobiology of stress and anxiety, I am encouraged by some of the preliminary research. For example, pre-clinical studies show that CBD can reduce fear and anxiety-related behaviors in <a href="https://pubmed.ncbi.nlm.nih.gov/2162942/">mice</a>. Neuroimaging studies in humans show that CBD can reduce activity in the <a href="https://pubmed.ncbi.nlm.nih.gov/19124693/">amygdala and anterior cingulate cortex</a>, brain regions associated with stress and anxiety. Yet more research must take place before we can be certain.</p>
<figure class="align-center ">
<img alt="CBD products can be found all across the U.S." src="https://images.theconversation.com/files/369456/original/file-20201116-19-1x7haff.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/369456/original/file-20201116-19-1x7haff.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/369456/original/file-20201116-19-1x7haff.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/369456/original/file-20201116-19-1x7haff.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/369456/original/file-20201116-19-1x7haff.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/369456/original/file-20201116-19-1x7haff.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/369456/original/file-20201116-19-1x7haff.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Early evidence suggests CBD could help with inflammation and some arthritic conditions.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/news-photo/various-wellness-products-containing-full-spectrum-news-photo/1266349533?adppopup=true">Smith Collection/Gado via Getty Images</a></span>
</figcaption>
</figure>
<h2>What is CBD?</h2>
<p>CBD is only one of more than 100 cannabinoids and other molecules found in the marijuana plant (<em>Cannabis Sativa</em>). Cannabinoids are known as signaling molecules: They interact with other molecules in the body, including the brain. For example, THC, the plant’s most abundant cannabinoid, interacts with brain receptors to cause the “high” feeling. Cannabinoids can also impact the immune system; this may help alleviate inflammation, arthritic conditions and neuropathic pain. </p>
<p>CBD, the plant’s second most abundant cannabinoid, does not contain THC, and therefore does not have psychoactive effects. There is no high. CBD also doesn’t seem to bind strongly with typical cannabinoid receptors. Instead, it interacts with other signaling molecules <a href="https://doi.org/10.1002/prp2.682">in the brain and throughout the body</a>. For example, CBD may act on the serotonin system, particularly serotonin <a href="https://doi.org/%2010.1097/j.pain.0000000000001386">5-HT1A receptors</a>, which are involved in signaling pathways that regulate pain, depression and anxiety.</p>
<p><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1573017/">Evidence suggests</a> that CBD may interact with the body’s own natural cannabinoid system – the endocannabinoid system – to boost levels of anandamide, the <a href="https://www.sciencedirect.com/topics/neuroscience/anandamide">“bliss molecule,”</a> our body’s natural version of THC, perhaps changing the way people think and feel. And CBD may act with the body’s natural <a href="https://pubmed.ncbi.nlm.nih.gov/33169541/">opioid system</a>. This would explain some of the reported pain-relieving qualities. Yet with all of these potential effects, we still don’t understand how CBD works to alleviate pain, anxiety, inflammation and even epilepsy, the only disorder for which a drug containing CBD has been FDA-approved. </p>
<p>In medicine, to see if something works, a randomized placebo-controlled trial is the gold standard. <a href="https://clinicaltrials.gov/ct2/results?cond=anxiety&term=cbd&cntry=&state=&city=&dist=">Several clinical trials</a> are underway to see if CBD works for anxiety, COVID-19-induced stress, and for the treatment of anxiety disorders – worldwide, the <a href="https://doi.org/10.1017/S1121189X00001421">most common mental disorder</a>. There are several <a href="https://www.nami.org/About-Mental-Illness/Mental-Health-Conditions/Anxiety-Disorders">types of anxiety</a> disorders, including generalized anxiety, which relates to excess worrying about everyday life, and social anxiety disorder, which includes intense fear around social interactions. Symptoms of anxiety can also vary, including feeling tense, irritable or jumpy, and also feeling that your heart is racing, sweating, headaches, stomachaches and insomnia. </p>
<p>Recent studies show that COVID-19 has exacerbated some already existing mental health problems. And, even for people without a history of mental health problems, <a href="https://doi.org/10.1016/S2215-0366(20)30462-4">a COVID-19 diagnosis increases</a> the risk of anxiety and other psychiatric disorders. </p>
<p>Preliminary and recent studies on the potential for CBD to reduce stress and anxiety <a href="https://doi.org/10.1089/can.2019.0052">are promising</a>. <a href="https://doi.org/10.1038/npp.2011.6">Two small preliminary studies</a>, for instance, tested whether CBD reduced anxiety in individuals with social anxiety disorder and in healthy volunteers. A public speaking test was simulated; those given CBD reported lower anxiety compared to those given a placebo (sugar pill). But we must wait for results of larger clinical trials to know if CBD works, and under what conditions. </p>
<figure class="align-center ">
<img alt="Dozens of food products laced with marijuana or CBD are on the market." src="https://images.theconversation.com/files/369361/original/file-20201113-21-16l76xt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/369361/original/file-20201113-21-16l76xt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=450&fit=crop&dpr=1 600w, https://images.theconversation.com/files/369361/original/file-20201113-21-16l76xt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=450&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/369361/original/file-20201113-21-16l76xt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=450&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/369361/original/file-20201113-21-16l76xt.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=566&fit=crop&dpr=1 754w, https://images.theconversation.com/files/369361/original/file-20201113-21-16l76xt.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=566&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/369361/original/file-20201113-21-16l76xt.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=566&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Dozens of marijuana or CBD-laced food products are now available.</span>
<span class="attribution"><a class="source" href="https://www.gettyimages.com/detail/photo/marijuana-brownies-royalty-free-image/1185895952?adppopup=true">Lauri Patterson via Getty Images</a></span>
</figcaption>
</figure>
<h2>Popularity outpaces science</h2>
<p>In November, voters in four states – Arizona, Montana, New Jersey and South Dakota – <a href="https://www.cnbc.com/2020/11/04/voters-chose-to-legalize-tax-recreational-marijuana-in-these-4-states.html">voted</a> to join 11 other states to legalize recreational cannabis use in the U.S. But the rise in legalization and decriminalization of cannabinoids, along with their widespread popularity, significantly outpaces the science. There is more research today on the potential medical applications of cannabinoids than ever before – including $196 million from the <a href="https://report.nih.gov/categorical_spending.aspx">National Institutes of Health</a>, along with $31 million on CBD in the year 2020.</p>
<p>Still, this is a relatively new area of medical research. CBD was discovered in 1940; the body’s own endocannabinoid system wasn’t discovered until 1992. This is shocking given that humans have been using cannabis and cannabis-based products for thousands of years. Evidence suggests medical use of cannabis dates back to ancient times, including around 2700 B.C., when Emperor Shen Nung – known as the father of Chinese medicine – was exploring cannabis use to treat over 100 different ailments, including <a href="https://books.google.com/books?hl=en&lr=&id=1AWGDhIOvk0C&oi=fnd&pg=PA35&dq=History+of+Therapeutic+Cannabis&ots=a3wpiboMDk&sig=sKYx899iOcrohVJjx4GoO_Cve3s#v=onepage&q=History%20of%20Therapeutic%20Cannabis&f=false">gout, rheumatism and malaria</a>.</p>
<p>But today, doctors, nurses and other medical providers are <a href="https://doi.org/10.1001/jamainternmed.2019.1529">generally not well prepared</a> to answer patients’ questions about potential risks, benefits and applications. This may be because cannabis and CBD are not a part of standard medical education. For example, a 2017 survey of medical residents and fellows in St. Louis found that 84.9% reported receiving no medical education about cannabis. </p>
<p>Government restrictions also contribute to the lag. Cannabis is still illegal at the federal level. In 2016, the U.S. Drug Enforcement Administration <a href="https://www.deadiversion.usdoj.gov/schedules/marijuana/Maintaining%20Marijuana%20in%20Schedule%20I%20of%20the%20Controlled%20Substances%20Act.pdf">affirmed</a> its classification of cannabis as a Schedule I drug. That put it in the same category as deadly and addictive drugs: opioids (like heroine and oxycodone). This is in stark contrast to research that shows cannabis is relatively safe and with a low potential for abuse. But because of this federal classification, scientific and medical study of cannabis is tightly regulated. Researchers need a special license from the DEA to study it. Physicians may also feel poorly trained because more and higher-quality research is needed before they make <a href="https://doi.org/10.1001/jamainternmed.2019.1529">recommendations</a> to their patients. </p>
<p>[<em>Deep knowledge, daily.</em> <a href="https://theconversation.com/us/newsletters/the-daily-3?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=deepknowledge">Sign up for The Conversation’s newsletter</a>.]</p>
<p>Researching CBD and other cannabis derivatives is also difficult. CBD products are currently unregulated by the U.S. Food and Drug Administration. This means CBD is not considered a dietary supplement, and marketed CBD products cannot make any health-related claims. This also means there’s no oversight on what’s in CBD products, which is why they are <a href="https://doi.org/10.1001/jama.2017.11909">frequently mislabeled</a>. This creates a “Wild West” environment for consumers. </p>
<p>So should you try CBD for stress and anxiety? The bottom line: It’s too early to tell. Those CBD gummies might just be an expensive placebo. In the meantime, turn to <a href="https://www.ajpmonline.org/article/S0749-3797(19)30246-6/fulltext">evidence-based treatments</a> for stress and anxiety relief – like good old-fashioned exercise.</p><img src="https://counter.theconversation.com/content/149612/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Dr. Marusak is supported, in part, by grants from the National Institute of Mental Health. </span></em></p>The jury’s still out on whether or not CBD relieves stress and anxiety.Hilary A. Marusak, Assistant Professor, Wayne State UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1188042019-07-25T12:55:03Z2019-07-25T12:55:03ZCBD and genetic testing provide hope for ‘intractable’ epilepsy in children<figure><img src="https://images.theconversation.com/files/282921/original/file-20190705-51258-fawlut.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A child with epilepsy during a seizure.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/download/success?u=http%3A%2F%2Fdownload.shutterstock.com%2Fgatekeeper%2FW3siZSI6MTU2MjM4ODExNywiYyI6Il9waG90b19zZXNzaW9uX2lkIiwiZGMiOiJpZGxfMTAyMzEzNzEzNyIsImsiOiJwaG90by8xMDIzMTM3MTM3L2h1Z2UuanBnIiwibSI6MSwiZCI6InNodXR0ZXJzdG9jay1tZWRpYSJ9LCJPcUxIZUlQakJxMStEVGVkUFd6ZjhyZ2ZzVDAiXQ%2Fshutterstock_1023137137.jpg&pi=33421636&m=1023137137&src=pzfZOgU7zal9-hDGIZqOKg-1-59">www.shutterstock.com</a></span></figcaption></figure><p>It can start with a vacant stare, what appear to be muscle twitches or a full-blown seizure. But no matter how it begins, any time a child is diagnosed with epilepsy is often a frightening time for families.</p>
<p>About <a href="https://www.cdc.gov/epilepsy/data/index.html">470,000 children are living with epilepsy</a> in the U.S. While there are over a dozen anti-seizure medications that can be prescribed, approximately <a href="https://www.massgeneral.org/childhood-epilepsy/medical/treatment.aspx">30%</a> of children don’t respond. These children have what medical professionals call intractable, or uncontrollable, epilepsy.</p>
<p><a href="https://scholar.google.com/citations?user=RQGyTlAAAAAJ&hl=en">As a postdoctoral scholar</a> in the lab of <a href="http://www.dullalab.org/">Chris Dulla</a> at the Sackler School of Graduate Biomedical Sciences at Tufts University, I focus on researching a form of epilepsy called infantile spasms. These spasms in infants can develop into intractable epilepsy and other more severe forms if the seizures are not stopped.</p>
<p>Recently, promising advances have been made in the field of epilepsy treatment with the development of cannabidiol-derived <a href="https://theconversation.com/approval-of-drug-derived-from-cannabis-not-necessarily-a-win-for-weed-99018">drugs</a> and the rise of genetic testing. I believe these advances are paving the way to provide treatment options for children with intractable epilepsy.</p>
<h2>What is childhood epilepsy?</h2>
<p>Epilepsy is <a href="https://www.ilae.org/guidelines/definition-and-classification/definition-of-epilepsy-2014">usually diagnosed</a> when a person has two or more seizures, greater than 24 hours apart. Medically, a seizure is defined as when abnormal electrical activity occurs in the brain but to an average person it sometimes can be difficult to detect. It might look like a blank stare, or in the case of infantile spasms, muscle twitching. Other times it might be easy to spot because the individual may collapse and shake.</p>
<p>Epilepsy can be genetic; there are over <a href="https://www.nature.com/articles/nrdp201824">500 genes</a> that have been associated with the disorder. </p>
<p>The most common type of childhood epilepsy, <a href="https://www.epilepsy.com/learn/types-epilepsy-syndromes/juvenile-myoclonic-epilepsy">juvenile myoclonic epilepsy</a> (JME), tends to be inherited from family members but at least 50% of individuals with JME do not have mutations in genes associated with epilepsy. This makes JME hard to treat, because without a mutation to help guide treatment options, doctors may have to test multiple medications before finding one that stops the seizures. JME can also be intractable.</p>
<p>Epilepsy can also be caused by traumatic brain injury, infection, fevers and autoimmune disease, known as acquired epilepsy. In about <a href="https://www.epilepsy.com/learn/professionals/about-epilepsy-seizures/idiopathic-generalized-epilepsies">30%</a> of all people, a cause for epilepsy cannot be identified. </p>
<p>Intractable epilepsy is particularly vexing for researchers and families. It is diagnosed after a physician has usually tried multiple anti-seizure drugs (ASD) without success. Sometimes, ASDs can decrease seizure frequency, but not completely stop them from occurring. In these cases, children still might be prescribed medication as well as alternative treatment options. </p>
<h2>How Do We Treat Epilepsy?</h2>
<p>In childhood epilepsy, it is especially important to diagnose and stop seizures as soon as possible because their severity can worsen over time and cause <a href="https://www.massgeneral.org/childhood-epilepsy/medical/diagnosis.aspx">developmental delays</a>. </p>
<p>Many ASDs act by decreasing the excitability in the brain. But some individuals can become tolerant to their ASDs over time, making the drugs ineffective. The exact reasons for this remain unclear. Severe side effects can also include mood swings, irritability, vision impairment and sleepiness. </p>
<p>Many ASDs also have to be taken multiple times a day. In children, this can make it difficult to stick to a treatment because it becomes disruptive to daily life.</p>
<p>Yet there is hope for children whose drugs stop working, or who have intractable epilepsy.</p>
<p>One increasingly prescribed therapy is the <a href="https://journals.sagepub.com/doi/10.5698/1535-7597-13.2.103">ketogenic diet</a>. This is a medically prescribed, strict, high-fat diet that is an alternative treatment for children with intractable epilepsy. Researchers do not know exactly why the ketogenic diet stops seizures. It is <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902940/">thought</a> that eating a 4:1 ratio of fat to carbohydrate forces the body to burn molecules called ketones for energy instead of carbohydrates. While this diet is effective, food preparation is very time-consuming and children may not stick to it because they cannot enjoy many popular snack foods.</p>
<h2>Advances in epilepsy treatment</h2>
<p>Advances in genetic testing technology have allowed for more genetic mutations to be identified in children with epilepsy. This can enable doctors to select ASDs that target specific mutations. Genetic screens could also identify previously undiscovered mutations associated with epilepsy and help lead to new drug development.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/282919/original/file-20190705-51258-13olxus.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/282919/original/file-20190705-51258-13olxus.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=411&fit=crop&dpr=1 600w, https://images.theconversation.com/files/282919/original/file-20190705-51258-13olxus.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=411&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/282919/original/file-20190705-51258-13olxus.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=411&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/282919/original/file-20190705-51258-13olxus.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=517&fit=crop&dpr=1 754w, https://images.theconversation.com/files/282919/original/file-20190705-51258-13olxus.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=517&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/282919/original/file-20190705-51258-13olxus.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=517&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A parent holds up a bottle of cannabis-infused oil used to treat her 4-year-old daughter who suffers from severe epilepsy.</span>
<span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Medical-Marijuana-Kids/9db7d65d723f422c90030ddc57e7ac67/48/0">Brennan Linsley/AP</a></span>
</figcaption>
</figure>
<p>Recently, the use of CBD derivatives has gained popularity as a treatment for intractable epilepsy. These CBD products are derived from hemp plants and do not contain psychoactive compounds. They have been <a href="https://www.nejm.org/doi/10.1056/NEJMoa1611618">shown</a> to be effective in reducing seizures but it was not until last year that the Food and Drug Administration approved a CBD drug for childhood epilepsy, called Epidiolex. While the exact mechanism of action for CBD is unknown, it is thought to generally <a href="https://www.gwpharm.com/healthcare-professionals/research/mechanism-action#">increase inhibition</a> of brain cell activity to stop seizures. </p>
<p><a href="https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-comprised-active-ingredient-derived-marijuana-treat-rare-severe-forms">Epidiolex</a> has less severe side effects compared to current ASDs and is effective in reducing seizures in two types of intractable epilepsy. A 2019 <a href="https://www.nature.com/articles/s41598-019-44056-y">study</a> also showed that H2CBD, a similar drug, is able to reduce seizures with the same efficacy as CBD. This study, however, was only done on rats and much more research is needed before it is known if it will work on children with intractable epilepsy.</p>
<p>In 2019, the FDA <a href="https://www.ucb.com/stories-media/Press-Releases/article/UCB-announces-NAYZILAM-midazolam-nasal-spray-now-approved-by-FDA-to-treat-intermittent-stereotypic-episodes-of-frequent-seizure-activity-in-people-living-with-epilepsy-in-the-U-S">approved</a> a new form of a previously approved ASD. Midazolam was already approved for use in adults in pill form but is now available as a nasal spray for adolescents. It treats <a href="https://www.ncbi.nlm.nih.gov/pubmed/10488906">seizure clusters</a>, which is a seizure emergency that can occur in children with intractable epilepsy. This is the first new medication that has been approved for this disorder in the United States in over 20 years. </p>
<p>[<em>Understand new developments in science, health and technology, each week.</em> <a href="https://memberservices.theconversation.com/newsletters/?nl=science&source=inline-science-understand">Subscribe to The Conversation’s science newsletter</a>.]</p>
<p>It has been over 100 years since the first ASD was developed, and there is much more that needs to be done in treating and curing juvenile epilepsy. Some children can grow out of their medication, but others may need to take medications for their entire lives. </p>
<p>However, with the increased use of genetic screens and the approval of new drugs, like Epidiolex, there is hope that one day we can stop seizures and cure childhood epilepsy.</p><img src="https://counter.theconversation.com/content/118804/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Isabel Derera does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>About 470,000 children in the US have epilepsy. Promising advances are being made in the field of epilepsy treatment for children.Isabel Derera, Postdoctoral Scholar, Tufts UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1176342019-05-28T10:46:37Z2019-05-28T10:46:37ZCBD: The next weapon in the war against opioid addiction?<figure><img src="https://images.theconversation.com/files/276413/original/file-20190524-187157-1qplu57.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A new study suggests that CBD could help curve cravings in people who have an opioid use disorder.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/syringe-marijuana-on-wooden-background-concept-1143223706?src=MKtoqNeVTWF6mKI2hUpGog-1-87">Evgenly Goncharov photo/Shutterstock.com</a></span></figcaption></figure><p>CBD, or cannabidiol, is everywhere, with word on the street saying that it can cure everything from a bad mood to cancer. However, most of these claims are not based on scientific evidence. Animal studies suggest that CBD might be beneficial for some health indications, such as <a href="https://journals.lww.com/pain/fulltext/2019/01000/Cannabidiol_modulates_serotonergic_transmission.16.aspx">pain</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828614/">inflammation</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4851925/">arthritis</a> and <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604171/">anxiety</a>. </p>
<p>However, until recently, the only medical indication that CBD has been proven to treat in humans is <a href="https://www.sciencedirect.com/science/article/pii/S0140673618301363?via%3Dihub">seizures associated with pediatric epilepsy</a>. Now, however, a <a href="https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2019.18101191">recent study</a> suggested that CBD curbed cravings in people with opioid dependence. This is one of the first double-blind controlled trials, the gold standard for drug research, to show benefit of using CBD outside epilepsy treatment. Thus, researchers can say with greater confidence that CBD may be helpful in fighting the war against opioid addiction.</p>
<p>While this study is very exciting, as scientists who study drugs and addiction, we want to stress that this study was very narrow and used specific, standardized amounts of CBD. Thus, the results do not suggest that buying a bottle or jar of over-the-counter CBD is going to help with opioid cravings – or any other medical conditions.</p>
<h2>Addiction is a brain disease</h2>
<p>In order to understand why CBD might be useful to treat opioid addiction, it is helpful to take a closer look at how addiction alters normal behavior. Addiction is broadly defined by the <a href="https://www.psychiatry.org/patients-families/addiction/what-is-addiction">American Psychiatric Association</a> as “a complex condition, a brain disease that is manifested by compulsive substance use despite harmful consequence.” <a href="https://www.drugabuse.gov/related-topics/addiction-science">Addiction is classified as a disease</a> because addiction hijacks and alters the way how the brain processes information. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/276404/original/file-20190524-187176-1pas1j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/276404/original/file-20190524-187176-1pas1j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=416&fit=crop&dpr=1 600w, https://images.theconversation.com/files/276404/original/file-20190524-187176-1pas1j.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=416&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/276404/original/file-20190524-187176-1pas1j.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=416&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/276404/original/file-20190524-187176-1pas1j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=523&fit=crop&dpr=1 754w, https://images.theconversation.com/files/276404/original/file-20190524-187176-1pas1j.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=523&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/276404/original/file-20190524-187176-1pas1j.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=523&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">People with opioid addiction issues can often be triggered by seeing drug paraphernalia, which can trigger a relapse.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/drug-paraphernalia-preparation-injection-cocaine-spoon-152099882?src=GkkYxUg_SrQV2uxb8pBlhA-1-15">Oleg Mikhaylov/Shutterstock.com</a></span>
</figcaption>
</figure>
<p>Specifically, areas of the brain critical in controlling the perception of daily and pleasurable activities are <a href="https://www.nature.com/articles/35094560">susceptible</a> to the influence of addictive drugs. Due to the rewiring of the brain under addiction, the individual often perceives the world in context to their drug of choice. The brain learns to associate drug paraphernalia or the physical location of drug partaking in the context of receiving a drug. These cues become integral reminders and reinforcers of drug use.</p>
<p>These events occur with most known drugs of abuse, such as <a href="https://www.drugabuse.gov/drugs-abuse/cocaine">cocaine</a>, <a href="https://www.niaaa.nih.gov/alcohol-health/overview-alcohol-consumption/alcohol-use-disorders">alcohol</a>, <a href="https://www.drugabuse.gov/drugs-abuse/tobacconicotine-e-cigs">nicotine</a>, <a href="https://www.drugabuse.gov/drugs-abuse/methamphetamine">methamphetamines</a> as well as <a href="https://www.drugabuse.gov/drugs-abuse/opioids">opioids</a>. </p>
<p>Addiction is often thought of in terms of the pursuit of the “high” associated with the use of a drug. However, most addicts continue to use, or relapse when trying to quit using their respective addictive drug. This difficulty, despite the desire and often pressure by friends, family and co-workers to quit, is often due to the negative effects of drug withdrawal. </p>
<p>Depending on the drug, the symptoms of drug withdrawal can vary and range from mild to severe intensity. In the case of opioid withdrawal, <a href="https://www.ncbi.nlm.nih.gov/pubmed/7841858">symptoms</a> often include anxiety, nausea, vomiting, diarrhea, abdominal cramps and rapid heartbeat. An individual going through opioid withdrawal experiencing extreme conditions of anxiety is likely to take opioids to alleviate that anxiety. This sort of behavior can be repetitive, leading to a what is called a feed-forward loop of dependence on an abused drug. </p>
<p>A person is often referred to as “<a href="https://www.drugabuse.gov/publications/teaching-packets/neurobiology-drug-addiction/section-iii-action-heroin-morphine/8-definition-dependence">dependent</a>” on a drug when the drug must be present for the individual to function normally. Importantly, <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206504/">anxiety and depression are correlated</a> with opioid dependence. </p>
<p>For dependent individuals, ongoing use of a drug is not perceived as a conscious choice, but rather an evil necessity. <a href="https://www.fda.gov/drugs/information-drug-class/information-about-medication-assisted-treatment-mat">Medication-assisted treatment</a> with drugs like methadone or buprenorphine, allows for an individual to undergo recovery from an opioid use disorder. The use of medication assisted treatment <a href="https://www.nejm.org/doi/full/10.1056/NEJMp1402780">significantly decreases</a> the likelihood of an individual to relapse and fatally overdose due to withdrawal or dependence symptoms.</p>
<h2>CBD and Epidiolex</h2>
<p>CBD was tested in several clinical trials and was shown to work and to be safe in treating a rare form of epilepsy. A pharmaceutical grade CBD, Epidiolex, gained FDA approval in June 2018 for this specific usage.</p>
<p>CBD is currently only prescribed as the drug Epidiolex. That is because, up until now, CBD has only been shown to be safe and effective in the treatment of intractable pediatric epilepsy.</p>
<p>Importantly, CBD binds to different receptors than those that lead to opioid addiction.</p>
<h2>CBD and opioid addiction</h2>
<p>In <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829756/">experiments reported in 2009</a>, rats were trained to press a lever to receive heroin. CBD did not decrease the amount of heroin that the rats self-administered, or the drug seeking behavior displayed by the rat while taking heroin. However, when rats were taken off heroin and given CBD, there was a decrease in drug-seeking behavior when the animals were exposed to a heroin-associated cue.</p>
<p><a href="https://www.ncbi.nlm.nih.gov/pubmed/25748562/">Initial studies</a> of CBD in humans verified that CBD, when co-administered with fentanyl, is safe and well tolerated in healthy, non-opioid dependent individuals. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604178/">A 2015 report</a> of a small double-blind study conducted in opioid-dependent individuals found that a single administration of CBD, in comparison to a placebo, decreased cue-induced craving of opioids and feelings of anxiety. A double-blind, placebo-controlled study means that doctors and patients in the study do not know who is getting a real drug and who is getting a placebo. That is to guard against what is known as the placebo effect. </p>
<p>A <a href="https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2019.18101191">double-blind placebo-controlled study</a> published on May 21, 2019 adds to these findings by demonstrating that the Food and Drug Administration-approved Epidiolex can reduce cue-induced craving in individuals that had been former heroin users. Furthermore, in these individuals, Epidiolex reduced reports of anxiety, and blood levels of <a href="https://www.sciencedirect.com/science/article/pii/S0306453005000831">cortisol</a>, a hormone known to increase under conditions of stress and anxiety. </p>
<p>Although further studies are needed, these studies strongly suggest that Epidiolex or CBD may hold promise as a critical weapon in fighting the opioid epidemic.</p>
<p>This could be a big deal.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/276414/original/file-20190524-187176-6681bs.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/276414/original/file-20190524-187176-6681bs.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=413&fit=crop&dpr=1 600w, https://images.theconversation.com/files/276414/original/file-20190524-187176-6681bs.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=413&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/276414/original/file-20190524-187176-6681bs.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=413&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/276414/original/file-20190524-187176-6681bs.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=519&fit=crop&dpr=1 754w, https://images.theconversation.com/files/276414/original/file-20190524-187176-6681bs.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=519&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/276414/original/file-20190524-187176-6681bs.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=519&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">A bottle of CBD oil may contain unpredictable amounts of CBD, and it also could contain THC.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/cbd-oil-on-wood-background-cannabis-1197389848?src=R24CmcqRrOHEDVxFGwGSYQ-1-53">WIRACHAI/Shutterstock.com</a></span>
</figcaption>
</figure>
<h2>Practical considerations</h2>
<p>Before rushing out to purchase over-the-counter CBD to treat any medical condition, there are several practical considerations that should be considered. </p>
<p>Only Epidiolex is FDA-approved for a medical condition – pediatric seizures. All other forms of CBD aren’t regulated. There have been numerous <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5818782/">consumer reports</a> that show that the actual amount of CBD in over-the-counter products is significantly less than what is reported on the label. Also, some of these over-the-counter products <a href="https://fox8.com/2019/05/15/missouri-school-employee-says-cbd-oil-caused-her-to-fail-drug-test-lose-job/">contain enough THC</a> to show up on drug tests. </p>
<p>Although Epidiolex was found to be safe in clinical trials, it can <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6175436/">interact</a> with other drugs prescribed for migraines and bipolar disorder. This could mean that taking CBD with certain drugs could diminish or enhance the effects of prescriptions, leading to problems controlling particular medical conditions that were once well-managed, or increase side effects of the other medications. For this reason, it is incredibly important to talk to your doctor or pharmacist about potential drug interactions before using CBD.</p><img src="https://counter.theconversation.com/content/117634/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Jenny Wilkerson has received funding from the NIH. </span></em></p><p class="fine-print"><em><span>Lance McMahon receives funding from the NIH. </span></em></p>A study suggests that CBD could help treat people with opioid addiction. But before you go buy a bottle for any use, it’s important to know that it has been FDA-approved to treat only one disease.Jenny Wilkerson, Assistant Professor of Pharmacodynamics, University of FloridaLance McMahon, Professor and Chair of Pharmacodynamics, University of FloridaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1022892018-08-29T18:02:01Z2018-08-29T18:02:01ZBrain implant could stop epilepsy seizures<figure><img src="https://images.theconversation.com/files/234039/original/file-20180829-195328-f75rh5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/344282432?src=0qMPwIzLEtNMAGGfywpNHw-1-88&size=medium_jpg">SpeedKingz/Shutterstock</a></span></figcaption></figure><p>For many people who suffer from neurological disorders, such as epilepsy, there are no viable treatment options. In our <a href="http://advances.sciencemag.org/content/4/8/eaau1291">latest research</a>, we developed an implantable device that may one day offer relief. We show that the implant can treat problems in the brain, such as epileptic seizures, by delivering brain chemicals – known as neurotransmitters – directly to the cells in the brain that cause the problem.</p>
<p>The implant works by using an electric field to push neurotransmitters out of the device from an internal reservoir. This process, known as <a href="https://www.thoughtco.com/electrophoresis-definition-4136322">electrophoresis</a>, allows for precise control over the dose and timing of drug delivery, which is important for addressing intermittent disorders such as epilepsy. </p>
<p>This way of delivering drugs also has the advantage of not increasing the local pressure where the drug exits the device because the drug molecules are not in a solvent – they exit the device “dry”. This is important because it means the drug molecules (neurotransmitters in this case) can interact directly with the tissue surrounding the implant without causing damage to those cells or the surrounding tissue.</p>
<p>Researchers have <a href="http://advances.sciencemag.org/content/1/4/e1500039">previously shown</a> that this method for delivering drugs can be used to manage pain, with an implant that was placed in the spinal cord of rats. The novelty of our work, published in Science Advances, was to engineer an implant small enough to be implanted in the brain of mice. We also incorporated tiny sensors into the implant to allow us to monitor the local brain activity where the device was implanted. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/234041/original/file-20180829-195298-10bkxsr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/234041/original/file-20180829-195298-10bkxsr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=375&fit=crop&dpr=1 600w, https://images.theconversation.com/files/234041/original/file-20180829-195298-10bkxsr.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=375&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/234041/original/file-20180829-195298-10bkxsr.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=375&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/234041/original/file-20180829-195298-10bkxsr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=471&fit=crop&dpr=1 754w, https://images.theconversation.com/files/234041/original/file-20180829-195298-10bkxsr.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=471&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/234041/original/file-20180829-195298-10bkxsr.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=471&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">Neurotransmitters are the brain’s chemical messengers.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/download/confirm/432573415?src=dOOXsUyelZUo17hUgHiTKQ-1-1&size=medium_jpg">Andrii Vodolazhskyi/Shutterstock.com</a></span>
</figcaption>
</figure>
<p>Using the on-board sensors, we could see the onset of seizure-like activity in mice. After a seizure was detected, we told the implant to send out inhibitory neurotransmitters to the brain tissue at the centre of the seizures. The neurotransmitters tell the cells in that tissue to stop propagating the seizure message to other cells. This stopped the seizures.</p>
<p>After finding that we could stop seizures, we wanted to see if we could prevent seizures altogether, rather than stop them after they have started. To test this, we started delivering the neurotransmitters before a dose of seizure-inducing chemicals was injected into the brain with a separate implant. These experiments showed that our implant could prevent any seizure-like activity from happening.</p>
<h2>Platform technology</h2>
<p>We are very excited because this is the first time anyone has seen that an electrophoretic drug delivery device can stop or prevent seizure-like activity. Also, we see this as a platform technology that could be adapted to help treat many different neurological disorders including epilepsy, Parkinson’s disease and brain tumours.</p>
<p>It is important to note that, so far, this device has only been tested in mice and rats. Judging from the time it has taken for other technologies to go from this stage to widespread clinical use, it is likely to be at least a decade before this technology would be widely available for humans. During this time much work will be done to prove the long-term viability of these implants for treating epilepsy as well as other neurological disorders.</p><img src="https://counter.theconversation.com/content/102289/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Christopher Proctor receives funding from the University of Cambridge where he is a research associate and Borysiewicz Biomedical Sciences fellow in the Department of Engineering.
</span></em></p>New approach to preventing seizures proves effective in mice.Christopher Proctor, Research Associate in the Fabrication and Validation of Implantable Ion Pumps, University of CambridgeLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1012312018-08-10T10:37:57Z2018-08-10T10:37:57ZFlip a switch and shut down seizures? New research suggests how to turn off out-of-control signaling in the brain<figure><img src="https://images.theconversation.com/files/231381/original/file-20180809-30449-1vejssm.jpg?ixlib=rb-1.1.0&rect=257%2C12%2C3624%2C2561&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">In an epileptic brain, the neurons fire wildly.</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/human-brain-impulse-mixed-media-452290207">Sergey Nivens/Shutterstock.com</a></span></figcaption></figure><p>The brain is a precision instrument. Its function depends on finely calibrated electrical activity triggering the release of chemical messages between neurons.</p>
<p>But sometimes the brain’s careful balance is knocked out of control, as in <a href="https://www.epilepsy.com/learn/about-epilepsy-basics/what-epilepsy">epilepsy</a>. Electroencephalography, or <a href="https://www.mayoclinic.org/tests-procedures/eeg/about/pac-20393875">EEG</a>, visualizes a brain’s electrical activity and can reveal how an epileptic seizure diverges from the predictable wave pattern of typical brain activity.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/231337/original/file-20180809-30446-1x4fofp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/231337/original/file-20180809-30446-1x4fofp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/231337/original/file-20180809-30446-1x4fofp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=186&fit=crop&dpr=1 600w, https://images.theconversation.com/files/231337/original/file-20180809-30446-1x4fofp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=186&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/231337/original/file-20180809-30446-1x4fofp.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=186&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/231337/original/file-20180809-30446-1x4fofp.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=233&fit=crop&dpr=1 754w, https://images.theconversation.com/files/231337/original/file-20180809-30446-1x4fofp.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=233&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/231337/original/file-20180809-30446-1x4fofp.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=233&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The pattern of typical brain activity is very regular. During an epileptic seizure, the electrical activity erratically spikes.</span>
<span class="attribution"><span class="source">Rochelle Hines</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>But medicine still lacks a solution to epilepsy. There’s limited possibility of predicting a seizure, and no way to intervene even when you can predict. Although pharmaceuticals are available to people dealing with epilepsy, they are fraught with <a href="http://www.tandfonline.com/doi/full/10.1586/ern.10.71">side effects</a>, and they <a href="https://doi.org/10.3390/brainsci8040049">do not work for everyone</a>.</p>
<p>Working on a problem in <a href="https://www.hinesgroup.net">my neuroscience lab</a>, when I stop to imagine how frightening it could be to live with a brain out of control in this way, it really motivates me. Could there be a way to seize back control of these neurons gone rogue? I’ve been focusing on how a specific compartment within each brain cell <a href="https://doi.org/10.1038/s41467-018-05481-1">might be able to help us do just that</a>.</p>
<h2>An override switch for brain activity</h2>
<p>Ever since I was an undergraduate student, I’ve been fascinated with a part of the neuron called the axon initial segment. Each neuron contains this small compartment. It’s where a neuron “decides” to fire an electrical signal, sending a chemical message on to the next cell.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/231339/original/file-20180809-30467-16v50vs.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/231339/original/file-20180809-30467-16v50vs.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/231339/original/file-20180809-30467-16v50vs.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=925&fit=crop&dpr=1 600w, https://images.theconversation.com/files/231339/original/file-20180809-30467-16v50vs.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=925&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/231339/original/file-20180809-30467-16v50vs.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=925&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/231339/original/file-20180809-30467-16v50vs.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1162&fit=crop&dpr=1 754w, https://images.theconversation.com/files/231339/original/file-20180809-30467-16v50vs.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1162&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/231339/original/file-20180809-30467-16v50vs.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1162&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The axon initial segment receives signals from adjacent neurons and ‘decides’ whether its own neuron will fire an electrical signal in response.</span>
<span class="attribution"><span class="source">Rochelle Hines</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>There are specialized connections here that can exert powerful control; they can override the cell’s own “decision” about firing. This control mechanism exists to organize or pattern brain activity – a requirement for much of our behavior.</p>
<p>For example, in order to fall asleep your brain activity needs to wind down into a slow oscillation. In contrast, sharp concentration on a problem requires the pattern to pick up, producing a rapid oscillation. An <a href="https://doi.org/10.1001/jamapsychiatry.2015.0483">inability to produce and regulate these patterns</a> of brain activity has been related to numerous disorders of the brain.</p>
<p>When the axon initial segments of numerous neurons all receive a silencing signal at the same time, it results in a trough in the wave pattern of the EEG. This means that it quiets the brain’s activity, something that under normal conditions would be useful when moving between relaxed awake and sleep states.</p>
<p>If researchers could harness the power of these inhibitory connections, we could potentially reset the brain’s activity pattern whenever we want to. It could be a way to wrest back control in an epileptic brain.</p>
<h2>Molecules that mediate the message</h2>
<p>To begin understanding how to regulate this power of the axon initial segment, my colleagues and I first needed to understand the molecular partnerships at these connections. For inhibition to be effective at the axon initial segment, there needs to be the right equipment available to receive the signal. In the case of inhibition in the brain, this equipment is <a href="https://doi.org/10.1016/j.conb.2011.10.007">the GABA A receptor</a>.</p>
<p>With collaborators <a href="https://scholar.google.com/citations?hl=en&user=LP1GjaQAAAAJ&view_op=list_works&sortby=pubdate">Hans Maric</a> and <a href="http://www.rudolf-virchow-zentrum.de/en/research/research-groups/schindelin-group/research.html">Hermann Schindelin</a>, we identified a close and exclusive partnership between two proteins – the GABA A receptor α2 subunit and collybistin. Figuring out the close relationship between these two molecules answers some open questions about how proteins at inhibitory contact sites might be interacting. We knew that the GABA A receptor α2 subunit is found at the axon initial segment, but researchers didn’t understand how it gets there or is kept there. Collybistin could be key.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/231375/original/file-20180809-30470-1gzgil4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/231375/original/file-20180809-30470-1gzgil4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/231375/original/file-20180809-30470-1gzgil4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=342&fit=crop&dpr=1 600w, https://images.theconversation.com/files/231375/original/file-20180809-30470-1gzgil4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=342&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/231375/original/file-20180809-30470-1gzgil4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=342&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/231375/original/file-20180809-30470-1gzgil4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=430&fit=crop&dpr=1 754w, https://images.theconversation.com/files/231375/original/file-20180809-30470-1gzgil4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=430&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/231375/original/file-20180809-30470-1gzgil4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=430&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Together, the GABA receptor protein and collybistin work together to receive the message from the neurotransmitter GABA within this important part of the neuron.</span>
<span class="attribution"><span class="source">Rochelle Hines</span>, <a class="license" href="http://creativecommons.org/licenses/by-nd/4.0/">CC BY-ND</a></span>
</figcaption>
</figure>
<p>So now we thought that these two proteins could be working together at the axon initial segment. To take it further, my postdoctoral mentor <a href="https://scholar.google.com/citations?user=8G-86gkAAAAJ&hl=en">Stephen Moss</a> and I wanted to understand what implications this might have for connections at the axon initial segment, and ultimately how the brain works. To try to figure that out, we created a genetic mutation that resulted in the two proteins being unable to connect.</p>
<p>Neurons of mice with this mutation did, in fact, lose inhibitory connections onto the axon initial segment. Inhibitory connections onto other parts of brain cells remained intact, again supporting the idea that this protein partnership is exclusive, and specifically important at the axon initial segment. </p>
<p>Mice with this mutation experience seizures during development. When they grow into adults, these mice no longer show behavioral signs of seizure. In some forms of pediatric epilepsy, kids can also “outgrow” their seizures. So this mutation is extremely valuable in providing a possible model for human pediatric epilepsy. We hope it can help us understand more clearly what happens in the brain during epilepsy, and also to design and test better therapies, like the selective compound developed by <a href="https://www.astrazeneca.com/our-science/IMED.html">AstraZeneca whose scientists</a> also contributed to this project.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/231343/original/file-20180809-30461-15y51yr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/231343/original/file-20180809-30461-15y51yr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/231343/original/file-20180809-30461-15y51yr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=415&fit=crop&dpr=1 600w, https://images.theconversation.com/files/231343/original/file-20180809-30461-15y51yr.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=415&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/231343/original/file-20180809-30461-15y51yr.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=415&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/231343/original/file-20180809-30461-15y51yr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=521&fit=crop&dpr=1 754w, https://images.theconversation.com/files/231343/original/file-20180809-30461-15y51yr.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=521&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/231343/original/file-20180809-30461-15y51yr.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=521&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Understanding more about these molecules could help researchers design what is essentially an ‘off switch’ for a brain that’s firing out of control.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/skeleton-xray-brain-off-male-his-115340698">Jeff Cameron Collingwood/Shutterstock.com</a></span>
</figcaption>
</figure>
<h2>A quantitative but early step</h2>
<p>Neuroscientists have long speculated about the partnership between the GABA A receptor and collybistin. Now <a href="https://doi.org/10.1038/s41467-018-05481-1">our results, recently published in Nature Communications</a>, define it quantitatively.</p>
<p>While we know GABA A receptors – which respond to the neurotransmitter GABA – control inhibitory signaling, we’re still figuring out how it all works. GABA signaling is diverse, with various connection types that exert distinct control over cell firing – something else we need to work to understand. And dysfunction in GABA signaling is <a href="https://doi.org/10.3389/fnmol.2018.00132">involved in a number of other disorders</a> of the brain, too, in addition to epilepsy. </p>
<p>The ultimate goal of this research is to design treatments that might be able to control inhibitory connections at the axon initial segment. We’d like to be in charge of that switch, able to turn off the out-of-control neural firing seen during an epileptic seizure.</p>
<p>I am imagining life with epilepsy, and I am also imagining life without it.</p><img src="https://counter.theconversation.com/content/101231/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Rochelle Hines received funding from the Canadian Institute for Health Research as a postdoctoral fellow, and currently acts as a consultant for Rapid Dose Therapeutics, a relationship that is regulated by the University of Nevada Las Vegas. Her collaborator Stephen Moss serves as a consultant for AstraZeneca, a relationship that is regulated by Tufts University.</span></em></p>During epileptic seizures, neurons in the brain fire without rhyme or reason. New research identifies a possible way to wrest back control by stopping these signals before they can get started.Rochelle Hines, Assistant Professor of Psychology, University of Nevada, Las VegasLicensed as Creative Commons – attribution, no derivatives.