Category Archives: Neuroscience

Neuroscience

The changing nature of approvals what does the future hold? – PMLiVE

We will continue to see geographic and therapeutic rebalancing. Growth in sales volume is slowing in the US and Europe, while greater activity has been observed in Mainland China. Regulatory processes in Mainland China have become more streamlined, resulting in greater investment by global pharma companies and more approvals of innovative medicines. Therapeutically, oncology and rare diseases will likely remain attractive candidates for investment, while market failures for neuroscience and anti-infective therapies will continue to negatively affect investment in those areas.

Digital technologies and artificial intelligence are creating new opportunities to identify new targets, leverage real-world data, rapidly test hypotheses and support clinical decision-making. Along with this, however, comes new challenges such as integrating the data sources needed to support robust machine learning. Therefore, the industry needs to develop solutions that provide a single source of truth to inform the decision-making process.

Finally, 2019 is tracking to be on par with 2012 and 2017 for the highest number of CEO changes within pharma companies and has the second highest number of changes within thetop 12 pharma companies. With these significant leadership changes, we should expect to continue to see additional changes within the industry for at least the next few years.

The analysis from CMR International highlights important questions about the sustainability of the pharmaceutical industry and provides objective insights that can inform discussions about how to move forward. It will be important to use ever-more sophisticated data sets to continue to understand pharmas ongoing evolution.

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The changing nature of approvals what does the future hold? - PMLiVE

Neuroscience

DeepMind Discovers AI Training Technique That May Also Work In Our Brains – Unite.AI

The human brain often recalls past memories (seemingly) unprompted. As we go throughout our day, we have spontaneous flashes of memory from our lives. While this spontaneous conjuration of memories has long been of interest to neuroscientists, AI research company DeepMind recently published a paper detailing how an AI of theirs replicated this strange pattern of recall.

The conjuration of memories in the brain, neural replay, is tightly linked with the hippocampus. The hippocampus is a seahorse-shaped formation in the brain that belongs to the limbic system, and it is associated with the formation of new memories, as well as the emotions that memories spark. Current theories on the role of the hippocampi (there is one in each hemisphere of the brain), state that different regions of the hippocampus are responsible for the handling of different types of memories. For instance, spatial memory is believed to be handled in the rear region of the hippocampus.

As reported by Jesus Rodriguez on Medium, Dr. John OKeefe is responsible for many contributions to our understanding of the hippocampus, including the hippocampal place cells. The place cells in the hippocampus are triggered by stimuli in a specific environment. As an example, experiments on rats showed that specific neurons would fire when the rats ran through certain portions of a track. Researchers continued to monitor the rats even when they were resting, and they found that the same patterns of neurons denoting a portion of the maze would fire, although they fired at an accelerated speed. The rats seemed to be replaying the memories of the maze in their minds.

In humans, recalling memories is an important part of the learning process, but when trying to enable AI to learn, it is difficult to recreate the phenomenon.

The DeepMind team set about trying to recreate the phenomenon of recall using reinforcement learning. Reinforcement learning algorithms work by getting feedback from their interactions with the environment around them, getting rewarded whenever they take actions that bring them closer to the desired goal. In this context, the reinforcement learning agent records events and then plays them back at later times, with the system being reinforced to improve how efficiently it ends up recalling past experiences.

DeepMind added the replaying of experiences to a reinforcement learning algorithm using a replay buffer that would playback memories/recorded experiences to the system at specific times. Some versions of the system had the experiences played back in random orders while other models had pre-selected playback orders. While the researchers experimented with the order of playback for the reinforcement agents, they also experimented with different methods of replaying the experiences themselves.

There are two primary methods that are used to provide reinforcement algorithms with recalled experiences. These methods are the imagination replay method and the movie replay method. The DeepMind paper uses an analogy to describe both of the strategies:

Suppose you come home and, to your surprise and dismay, discover water pooling on your beautiful wooden floors. Stepping into the dining room, you find a broken vase. Then you hear a whimper, and you glance out the patio door to see your dog looking very guilty.

As reported by Rodriguez, the imagination replay method doesnt record the events in the order that they were experienced. Rather, a probable cause between the events is inferred. The events are inferred based on the agents understanding of the world. Meanwhile, the movie replay method stores memories in the order in which the events occurred, and replays the sequence of stimuli spilled water, broken vase, dog. The chronological ordering of events is preserved.

Research from the field of neuroscience implies that the movie replay method is integral to the creation of associations between concepts and the connection of neurons between events. Yet the imagination replay method could help the agent create new sequences when it reasons by analogy. For instance, the agent could reason that if a barrel is to oil as a vase is to water, a barrel could be spilled by a factory robot instead of a dog. Indeed, when DeepMind probed further into the possibilities of the imagination replay method, they found that their learning agent was able to create impressive, innovative sequences by taking previous experiences into account.

Most of the current progress being made in the area of reinforcement learning memory is being made with the movie strategy, although researchers have recently begun to make progress with the imagination strategy. Research into both methods of AI memory can not only enable better performance from reinforcement learning agents, but they can also help us gain new insight into how the human mind might function.

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DeepMind Discovers AI Training Technique That May Also Work In Our Brains - Unite.AI

Neuroscience

Victorian underwear reveals what it is like to live with epilepsy – Epilepsy Society

Last year we posted a call out on social media, asking people with epilepsy to share their thoughts about what it is like to live with seizures.

Now the artist, Susan Aldworth has turned those testimonies into an innovative exhibition using both antique Victorian underwear and sophisticated technology to explore the impact that epilepsy has on peoples lives.

And the exhibition, Out of the Blue, opens this weekend on 18 January at Hatton Gallery Institute of Neuroscience, Newcastle. It will run until 9 May 2020.

The worst part is that no one else notices. It feels like Im going to explode but no one else sees a thing... Im just stuck, Im still conscious. I can see, feel, and think. But I cant do anything. Im trapped in a body that wont listen to me. Sophie

The exhibition is built around more than 100 pieces of Victorian underwear chemises, nightdresses, bloomers each embroidered by members of the Royal School of Needlework with extracts from individual testimonies.

The garments are stitched in ultraviolet yellow and light blue, and black. They are then suspended by the ceiling on pulleys programmed by computers to correspond to the algorithms of electrical activity in an epileptic brain.

Out of the Blue was commissioned by the Institute of Neuroscience at Newcastle University and is funded by the Wellcome Trust. Scientists at the institute are developing experimental treatments for epilepsy that use optogenetics, a biological technique that controls the activity of neurons in the brain, using light and genetic engineering.

The fluorescent embroidery is lit by both natural and ultraviolet light to reflect the scientists light-sensitive gene therapies.

After a seizure my head feels like it has been smashed against a brick wall and my whole body aches. My epilepsy nurse once told me she had a patient who was hit by a bus and they said that was less painful than a seizure.Willow

As an artist I really wanted to explore how it makes people feel to have epilepsy and what it is like to live with it, explains Susan. I wanted to give people with epilepsy a voice and bring the condition out into the open.

Almost 100 people responded to Susans request for personal testimonies, describing the reality of how they and their families are affected by the condition.

I was really blown away by their responses, says Susan. They described their lived experience of epilepsy with amazing candour and detail. Their testimonies are incredibly emotional and real.

You can read a full interview with Susan Aldworth in our members magazine, Epilepsy Review. Find out how you can become a member and get a copy of Epilepsy Review twice a year for free. https://www.epilepsysociety.org.uk/become-member-epilepsy-society

Out of the Blue is at Hatton Gallery Institute of Neuroscience, Newcastle and runs from 18 January 9 May 2020.

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Victorian underwear reveals what it is like to live with epilepsy - Epilepsy Society

Neuroscience

JPM: Biotech, VC execs on where the industry should look beyond cancer – FierceBiotech

SAN FRANCISCOOncology is clearly a major medical and societal issue: a major killer that, while predominately affecting the older population, can strike the young through a mixture of environmental factors or a genetic lottery. Its no wonder we struggle to even call it by its name, preferring just the "big C."

Biopharma has acted accordingly over the years and spent billions (and made many more billions) developing new oncology therapies, with the media and political focus falling on cancer drugs far more acutely than any other area, whether that be over pricing (the current average cost of a new cancer drug in the U.S. is around $100,000), effectiveness/safety or rejection from healthcare gatekeepers, such as the National Institute for Health and Care Excellence in England.

But cancer is only one disease area: Heart disease is the biggest killer in the U.S., yet there are very few new and innovative CV drugs out there, with influenza complications, such as pneumonia, Alzheimers disease, stroke and diabetes complications all leading causes of death in the U.S. There has been a war on cancer, but not a war on stroke.

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There is also the growing threat of antimicrobial resistance, where decades-old antibiotics are ceasing to work against common forms of bacteria as they evolve; this, coupled with the fact that most life science companies arent working on a next generation of antibiotics (R&D costs are high with little or no ROI), means we could very well be facing a new surge in deaths in the future from once preventable diseases and infections.

At the J.P. Morgan Healthcare Conference in San Francisco this week, we at FierceBiotech wondered what the industry was doing about this and asked a range of life science C-suite execs: What therapeutic areas beyond cancer are most important to the industry now? both in terms of unmet need as well as where there is some real innovation.

Jim Robinson, chief operating officer at Paragon Biosciences, said: I spent 10 years in oncology, so I understand that point. Still, the biggest issue we face today that has to be figured out is Alzheimers. Looking at the aftermath, its scaryits going to be trillions of dollars in 20 short years in terms of the expense treating patients with Alzheimers. In 20 short years, I might be one of those patients!

I think its been a vast wasteland of failure. Im hoping something comes about before Im 70 to allow us to treat it. Whether the industry is willing to shift more resources to pursue treatments or not remains to be seen, especially after the latest failures. I dont know if the industry will shift to Alzheimers or more CNS treatments associated with cognition, but Im hoping.

Oncology good news is when the industry shifted and thousands of drugs moved through development. We see a significant transformation in certain cancers. If the incentive or the approach from a regulatory pathway that shifts incentives to research in Alzheimers, we will find some answers.

The biotechs CEO, Jeff Aronin, who is also CEO of Paragon Capital Partners, echoed this need for answers. I have a focus there with one of our companies, but in general, I would answer a little broader, he explained. Ive been involved in CNS drug development for a very long time and remember the 90s, which they called the decade of the brain, but we really didnt make a lot of advances in neuroscience and psychiatry that we thought we would have.

I think over the next few years is where we are really going to see many medicines approved. We have learned so much more and advancing in many different areas. In neuroscience and psychiatry, I would add theyre also an area of tremendous cost to the healthcare system and we still dont have a lot of great solutions, whether its Alzheimers or any of the neuropsychiatry areas were working in.

BioNTechs Sean Marrett also saw Alzheimers and other neuroscience areas, such as Parkinsons disease, as still major and unmet issues, as well as multiple sclerosis, which has seen great strides but still needs work.

Alzheimers is certainly a major issue, but also one that is more entrenched in the west: We live longer and are therefore more susceptible to diseases associated with aging.

Lyndra Therapeutics CEO Patricia Hurter asked us whether we meant our question in relation to the developed world or the developing world? We asked her two cents on both.

Women in Africa either get pregnant or get HIV, she said starkly. Their economic prospects are horrendous. It means their childrens economic prospects are horrendous. Were working with Gilead on HIV prophylaxis and on an oral birth control. Eventually, when the drugs are potent enough, we could do a once-a-month pill of each. To have them in one capsulethat would be fabulous. That would be transformative for developing countries.

For America, I think so many things like hypertension and diabetes are a chronic epidemic and people are having bad health outcomes [that could be avoided] if they took well proven drugs in an adherent way. Its an adherence issue. Theyre not feeling sick so they dont take the medicine. But in fact, it is still progressing [it, referring to stuff like hypertension, NASH that progressively gets worse without you feeling sick until its advanced].

It leads to unnecessary hospitalizations. If we could combine modern methods of distribution that a poly-pill combination that a person neededonce a week they would take one thing to keep them from progressing.

Karuna Therapeutics CEO Steve Paul also pointed to suicide rates that keep going up, whereas in certain types of cancer and cardiovascular disease theyve started tracking down.

And, finally, Westlake Village Biopartners Managing Partner Sean Harper said: Because there are so many areas of unmet need, its hard to say just one therapeutic area or one modality. Its exciting: the cellular engineering thats going to result in the ability to do regenerative medicine type efforts is I think going to be the next really amazing sort of thing.

With the fact that you can manipulate human cells now the way you can, and make multiple difficult edits to engineer things out of them and so on, that is just a new frontier. There are a lot of settings where you can just imagine what that can do. Its not 100 years away. Its now. Its happening already, people are doing it. I think that, to me, is the most exciting area.

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JPM: Biotech, VC execs on where the industry should look beyond cancer - FierceBiotech

Neuroscience

Brain Mapping Instruments Market: Qualitative Analysis of the Leading Players and Competitive Industry Scenario, 2026 Dagoretti News – Dagoretti News

The utilization of brain mapping instruments has expanded because of increasing occurrences of brain ailments in different parts of the world. Increasing health concerns and enhanced healthcare infrastructure are a few of the foremost aspects driving the expansion of the worldwide market for brain mapping instruments. Furthermore, an increasing number of diagnostics centers is likewise driving the expansion of the market. Nonetheless, poor healthcare insurance coverage and high expenses related to the brain mapping procedure are limiting the expansion of the worldwide market for brain mapping instruments. Also, lack of helium for magnetic resonance imaging systems, saturation in mature markets and technological constraints related to independent systems are likewise constraining expansion of the worldwide market.

High affecting aspects, for example, continuous brain mapping investigation and examination projects, neuroscience-based activities by government bodies as well as technological progressions in algorithms and tools which are applied in neuroscience space are considered to enhance the market expansion. These variables are foreseen to support revenue generation by impelling the product implementation in this market over the years to follow.

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The existence of institutes & organizations, for example, NIH, University of Utah, NeuroScience Canada, Ontario Brain Institute, Max Planck Florida Institute, along with the University of Pennsylvania; in the space are anticipated to significantly affect the advancement of neuroscience field. These entities act a significant part in quickening neuroscience-based r&d to enhance patient results in those suffering from neurological ailments.

Various activities are embraced by the healthcare communities to take cerebrum related innovations and studies above and beyond. For example, in 2014, the University of Utah presented the Neuroscience Initiative keeping in mind the end goal to help mitigate the staggering impacts of brain disorders. The launch was made for developing the understanding of the impacts of brain disorders on wellbeing and channelizing the learning into inventive solutions for patient care.

Constant presentation of new products by prominent market players in the market to the battle different neurological issue will probably support the Y-O-Y development of this market. For example, in September 2015, Codman Neuro (functioning unit of DePuy Synthes) presented CODMAN CERTAS plus programmable valve, an MRI-safe programmable valve along with eight dissimilar weight settings.

Moreover, key aspects that have quickened the research studies about in this field is the development of a number of different harmful CNS issues, for example, Alzheimers and Parkinsonism sickness. As geriatric populace is inclined to different central sensory systems related disorders, for example, Alzheimers, schizophrenia and Parkinsonism with the rise in the aging populace, this market is foreseen to see lucrative development.

The requirement for minimally invasive, more precise along with manifold neuron recording system is additionally anticipated that would drive r&d of hardware and software utilized for neuro-scientific analyses. This, thusly, is considered to reinforce the overall product portfolio accessible in the market and enhance revenues all through the years to come.

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Enhancing healthcare infrastructure in developing nations, for example, India and China would generate prospects for the worldwide market for brain mapping instruments. Expanding implementation of refurbished diagnostic imaging systems would represent a challenge for expansion of the mind-brain mapping instruments market globally. A few of the foremost companies functioning in the global market are Philips Healthcare, GE Healthcare, Natus Medical, Inc and Siemens Healthcare. Other market players active in the market are Nihon Kohden Corporation, Covidien, PLC., and Advanced Brain Monitoring, Inc.

Partnerships and collaboration are preferred as a feasible strategy to remain competitory in the market by foremost companies. Companies are engrossed in strategic alliances outside the region and within the region, which helps the expansion of both the parties along with the connected regional market.

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Brain Mapping Instruments Market: Qualitative Analysis of the Leading Players and Competitive Industry Scenario, 2026 Dagoretti News - Dagoretti News

Neuroscience

Twenty-year Follow-up Study Finds Schizophrenia Medication To Be Safe – Technology Networks

Researchers at Karolinska Institutet in Sweden and their colleagues in Germany, the USA and Finland have studied the safety of very long-term antipsychotic therapy for schizophrenia. According to the study, which is published in the scientific journal World Psychiatry, mortality was higher during periods when patients were not on medication than when they were.

People with schizophrenia have an average life expectancy ten to twenty years below the norm, and there has long been concern that one of the causes is the long-term use of antipsychotic drugs. Earlier compilations (meta-analyses) of results from randomised studies, however, indicated that the mortality rate for people with schizophrenia on antipsychotic medication was 30 to 50 per cent lower than those who have received placebo.

However, most of the studies done have been shorter than six months, which does not reflect the reality of treatment often being life-long. Researchers from Karolinska Institutet and their international colleagues have now done a long-term follow-up, substantiating previous results and demonstrating that antipsychotic drugs are not associated with increased risk of co-morbid complications, such as cardiovascular disease. The study is the largest conducted in the field to date.

"It's difficult to make comparisons between people on permanent medication and those who aren't, as these groups differ in many ways," says Heidi Taipale, assistant professor at the Department of Clinical Neuroscience at Karolinska Institutet. "One common method of dealing with this has been to try to take account of such differences when making comparisons. However, we chose another method, in which each person was their own control, making it possible for us to make individual comparisons of hospitalisation during periods of antipsychotic medication and periods of no treatment."

The researchers monitored just over 62,000 Finns who had received a schizophrenia diagnosis at some time between 1972 and 2014. This they did by accessing various Finnish registries up until 2015, giving an average follow-up period of over 14 years. They found that the likelihood of being hospitalised for a somatic disease was just as high during the periods when the patients were on antipsychotic drugs as when they were not. The differences in mortality, however, were noticeable. The cumulative mortality rate in the follow-up period at periods of medication and non-medication was 26 and 46 per cent respectively.

The researchers believe that there is overwhelming support for continual antipsychotic treatment for schizophrenia being a safer option than no medication. At the same time, treatment brings the risk of adverse reactions, such as an increase in weight, which can raise the risk of cardiovascular disease. The finding that treatment with antipsychotic drugs does not increase the likelihood of hospitalisation for cardiovascular disease may be attributable, argue the researchers, to the fact that the drugs can also have an antihypertensive effect and can reduce anxiety and the risk of substance abuse. Antipsychotic treatment may also help patients adopt a healthier lifestyle and make them more likely to seek care when needed.

"Antipsychotics get something of a bad press, which can make it difficult to reach out to the patient group with information on how important they are," says Jari Tiihonen, professor of psychiatry at the Department of Clinical Neuroscience, Karolinska Institutet. "We know from previous studies that only half of those who have been discharged from hospital after their first psychotic episode with a schizophrenia diagnosis take antipsychotic drugs. Besides, there are many people with schizophrenia who are on long-term benzodiazepine medication, which is in breach of existing guidelines and is associated with increased mortality risk. Building trust and understanding towards the efficacy and safety of antipsychotic drugs is important, and we hope that this study can contribute to this end."

Reference: Taipale, H., Tanskanen, A., Mehtl, J., Vattulainen, P., Correll, C. U., & Tiihonen, J. (2020). 20-year follow-up study of physical morbidity and mortality in relationship to antipsychotic treatment in a nationwide cohort of 62,250 patients with schizophrenia (FIN20). World Psychiatry, 19(1), 6168. https://doi.org/10.1002/wps.20699

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Twenty-year Follow-up Study Finds Schizophrenia Medication To Be Safe - Technology Networks

Neuroscience

The Neuroscience of Behavior: Five Famous Cases – Psychology Today

Considering everything, it seems we are dealing here with a special illness There are certainly more psychiatric illnesses than are listed in our textbooks. Alois Alzheimer

Once thought to be the product of demonic possession, immorality, or imbalanced humors, we now know that psychiatric symptoms are often caused by changes in the brain. Read on to learn about the people who helped us understand the brain as the driving force behind our behaviors.

Artist renditions estimating the rod path through Phineas Gage's brain.

Source: By Henry Jacob Bigelow; Ratiu et al.

Phineas Gage

In 1848, John Harlow first described the case of a 25-year-old railroad foreman named Phineas Gage. Gage was a "temperate" man: hardworking, polite, and well-liked by all those around him. One day, Gage was struck through the skull by an iron rod launched in an accidental explosion. The rod traveled through the prefrontal cortex of his brain. Remarkably, he survived with no deficits in his motor functionor memory. However, his family and friends noticed major changes in his personality. He became impatient, unreliable, vulgar, and was even described as developing the "animal passions of a strong man." This was the first glimpse into the important role of the prefrontal cortex in personality and social behavior.

Louis Victor Leborgne

Pierre Broca first published thecase of 50-year-old Louis Victor Leborgne in 1861. Despite normal intelligence, Leborgne inexplicably lost the ability to speak. His nickname was Tan, after thisbecame the only word he ever uttered. He was otherwise unaffected and seemed to follow directions and understand others without difficulty. After he died, Broca examined his brain, finding an abnormal area of brain tissue only in the left anterior frontal lobe. This suggested that the left and right sides of the brain were not always symmetric in their functions, as previously thought. Broca later went on to describe several other similar cases, cementing the role of the left anterior frontal lobe (now called Brocas area) as a crucial region for producing(but not understanding)language.

Auguste Deter, 1901.

Source: Unknown, Public Domain.

Auguste Deter

Psychiatrist and neuropathologist Aloysius Alzheimer described the case of Auguste Deter, a 56-year-old woman who passed away in 1906 after she developed strange behaviors, hallucinations, and memory loss. When Alzheimer looked at her brain under the microscope, he described amyloid plaques and neurofibrillary tangles that we now know are a hallmark of the disease that bears his name. This significant discovery was the first time that a biological molecule such as a protein was linked to a psychiatric illness.

JP

In 1933, Spafford Ackerly described the case of "JP who, beginning at a very young age, would do crude things like defecate in other's belongings, expose himself, and masturbate in front of other children at school. These behaviors worsened as he aged, leading to his arrest as a teenager. He was examined by Ackerly who found that the boy had a large cyst, likely present from birth, that caused severe damage to his prefrontal cortices. Like the case of Phineas Gage, JP helped us understand the crucial role that the prefrontal cortex plays in judgement, decision making, social behaviors and personality.

HM (Henry Gustav Molaison)

HM was a 29-year-old man who underwent an experimental surgery by William Beecher Scovillein 1953 to remove his medial temporal lobes (including the hippocampus and amygdala on both sides). The hope was that the surgery would control his severe epilepsy, and it did seem to help. But with that improvement came a very unexpected side effect: HM completely lost the ability to form certain kinds of new memories. While he was still able to form new implicit or procedural memories (like tying shoes or playing the piano), he was no longer able to form new semantic or declarative memories (like someones name or major life events). This taught us that memories were localized to a specific brain region, not distributed throughout the whole brain as previously thought.

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The Neuroscience of Behavior: Five Famous Cases - Psychology Today

Neuroscience

Microglia: a new brain target for depression and Alzheimer’s? – STAT – STAT

More than a decade ago, I was diagnosed with a string of autoimmune diseases, one after another, including a bone marrow disorder, thyroiditis, and then Guillain-Barr syndrome, which left me paralyzed while raising two young children.

I recovered from Guillain-Barr only to relapse, becoming paralyzed again. My immune system was repeatedly and mistakenly attacking my body, causing the nerves in my arms, legs, and those I needed to swallow to stop communicating with my brain, leaving me confined to and raising my children from bed.

As I slowly began to recover and learn to walk again, I noticed that along with residual physical losses I had experienced shifts in my mood and clarity of mind. Although Id always been an optimistic person, I felt a bleak unshakable dread, which didnt feel like the old me.

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I also noticed cognitive glitches. Names, words, and facts were hard to bring to mind. I can still recall cutting up slices of watermelon, putting them in a bowl, and staring down at them thinking, What is this again? I knew the word but couldnt remember it. I covered my lapse by bringing the bowl to the table and waiting for my children to call out, Yay! Watermelon! And I thought, Yes. Of course. Watermelon.

As a science journalist whose niche spans neuroscience, immunology, and human emotion, I knew at the time that it didnt make scientific sense that inflammation in the body could be connected to much less cause illness in the brain. At that time, scientific dogma held that the brain was the only organ in the body not ruled by the immune system. The brain was considered to be immune privileged.

That began to change in the early 2010s. As neuroscience and immunology started to merge, they began dismantling that century-old tenet. Scientists pivoted away from believing that the brain and body function as church and state entities, and developed an entirely new brain-body paradigm which acknowledges that the brain is also governed by the immune system.

Much of the revelatory science fueling this reversal in how we see brain health was due to a radically new understanding of tiny cells called microglia. In healthy brains, microglia act as humble housekeepers, removing dead cells and bathing neurons in protective factors. A new understanding of these cells tells us that when they go rogue, they destroy synapses and cause inflammation in the brain.

In 2012, Beth Stevens, a young researcher at Childrens Hospital and Harvard Medical School, and her then-postdoc, Dori Schafer, discovered that microglia also determine synaptic health, for good or ill, from cradle to grave a discovery for which Stevens was named a 2015 MacArthur genius award winner. They showed that these cells, which scientists had ignored since they were first noted in the 1920s, were actually powerful immune cells.

But just as the bodys immune system can rev into overdrive, causing inflammation and devastating physical symptoms, microglia can also become overexcited. When that happens, they can generate too much synaptic pruning, neuroinflammation, and symptoms of cognitive, mood, and behavioral disorders, from depression to Alzheimers disease.

This revelation, while scary to contemplate if you are a patient like me, is also the springboard for promise with a newly emerging and innovative set of tools that may help intervene in mental health disorders by treating the brains immune pathways much as we treat immune disorders of the body.

It turns out that people who have high levels of chronic inflammation, as measured by simple blood tests, also have higher levels of microglial activation in the brain, a keen and worrisome indicator that too many synapses are being lost.

This month, four hospitals from the National Network of Depression Centers the Mayo Clinic, University of Michigan, Johns Hopkins Hospital, and Emory University are wrapping up a clinical trial known as the Bio-K Study. It is investigating whether measuring individuals levels of inflammation and other related biomarkers can predict if infusions of ketamine (the K in the study name) will ease their depression. Originally used as an anesthetic, ketamine has been shown to have powerful antidepressant effects, and appears to work as an anti-inflammatory in the brain.

The Bio-K study is fueled by recent discoveries that individual differences in patients physical health can affect how well a treatment for depression helps the brain repair itself. Of particular interest is how inflammation, which can signal microglia to become overactive and destroy synapses in areas of the brain related to symptoms of depression and bipolar disorder, might limit someones response to treatment.

The Bio-K investigators are measuring participants levels of chronic inflammation before they receive ketamine infusions. After the infusions, blood samples are checked again to determine if changes in biomarkers are associated with improved outcomes.

If the findings are positive, it will help clinicians determine if inflammation is associated with patients positive, neutral, or negative responses to treatment, and may help them predict which treatments are best for which patients.

At Emory University School of Medicine, researchers have found that inflammation is linked to weakened reward circuits in depression and they can predict which patients neural circuits are going dark by measuring their level of inflammation via a simple blood draw. Also underway at Emory are clinical trials looking at the viability of using the same anti-inflammatories employed to treat autoimmune disease, such as infliximab, to treat depression. The hope is that by getting overexcited microglia to back off, important regions of the brain will be able to communicate again.

This new understanding of the working of the immune system in the brain is also leading to a clearer understanding of which oral antidepressant will work best in which patient. It turns out that for individuals who test positive for chronic inflammation, bupropion (Wellbutrin) may work better than drugs like escitalopram (Lexapro).

Immunotherapy also appears to show promise in treating Alzheimers disease. Last spring, news broke that Enbrel, Pfizers powerhouse anti-inflammatory drug for rheumatoid arthritis, appeared to help prevent Alzheimers disease. In data collected by a computer analysis of over 250,000 insurance claims, the drug reduced the risk of Alzheimers disease by 64% in patients who took it.

Others have picked up this research thread, and a number of labs are targeting the ways microglia express genes that increase the risk of Alzheimers. Piggybacking on work by an international team of researchers who identified a genetic mutation that seems to protect people from developing Alzheimers disease, Alector, an early-stage biotech company, identified a drug candidate called AL014 that shifts microglial gene expression in ways that prompt microglia to turn from the dark side to the light and begin clearing the brain of unwanted toxins. In theory, that may help stave off the onset of Alzheimers.

Why mental health disorders can be so difficult to treat in some people and not others is a mystery. The idea that microglia-led inflammation triggered by a combination of genes and environmental factors from emotional trauma to toxins can slowly brew within the brain throughout an individuals lifetime offers a clue to that enigma.

When microglia go haywire, they destroy synapses and neural connections in the brain that affect mood and behavior. There can be many consequences: overreaction to small problems, a dearth of joy, entrenched depression, pernicious anxiety, forgetfulness, lost memories. No two individuals brains are the same.

Over time, many small changes in neurocircuitry wrought by inflammation-led microglia can cause individuals to feel and behave very differently from the persons they once were or the ones they hoped to become.

Although the excessive forgetfulness I experienced in my post-paralysis years no longer plagues me, its been replaced by the kind of age-related glitches we all face. Having once struggled to add simple numbers and recall familiar words, Im eager to avoid going through that again. So Im keeping an eye out for where these trials lead, bearing in mind the first rule of medicine: We must first be sure to do no harm, and proceed with an abundance of caution.

As I get older, will I be brave enough to try an anti-inflammatory to help calm down the microglia that govern the 3-pound jelly universe that is my brain? I have a little time to decide. But not too much.

Donna Jackson Nakazawa is a science journalist and author of six books, including The Angel and The Assassin: The Tiny Brain Cell That Changed the Course of Medicine (Random House/Ballantine, January 2020).

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Neuroscience

How Alcohol Addiction and Abstinence Remodel the Brain – Technology Networks

Employing advanced technologies that allow whole brain imaging at single-cell resolution, researchers at University of California San Diego School of Medicine report that in an alcohol-dependent mouse model, the rodent brain's functional architecture is substantially remodeled. But when deprived of alcohol, the mice displayed increased coordinated brain activity and reduced modularity compared to nondrinker or casual drinker mice.

The findings, published in the January 14, 2020 online issue of PNAS, also identified several previously unsuspected regions of the brain relevant to alcohol consumption, providing new research targets for better understanding and treatment of alcohol dependence in humans.

"The neuroscience of addiction has made tremendous progress, but the focus has always been on a limited number of brain circuits and neurotransmitters, primarily dopaminergic neurons, the amygdala and the prefrontal cortex," said senior author Olivier George, PhD, associate professor in the Department of Psychiatry at UC San Diego School of Medicine.

"Research groups have been fighting for years about whether 'their' brain circuit is the key to addiction. Our results confirm these regions are important, but the fact that we see such a massive remodeling of the functional brain architecture was a real shock. It's like studying the solar system and then discovering that there is an entire universe behind it. It shows that if you really want to understand the neurobiological mechanisms leading to addiction, you can't just look at a handful of brain regions, you need to look at the entire brain, you need to take a step back and consider the whole organ."

George said the findings further undermine the idea that addiction is simply a psychological condition or consequence of lifestyle. "You would be surprised at how prevalent this view remains," he said. "The brain-wide remodeling of the functional architecture observed here is not 'normal.' It is not observed in a nave animal. It is not observed in an animal that drinks recreationally. It is only observed in animals with a history of alcohol dependence and it is massive. Such a decrease in brain modularity has been observed in numerous brain disorders, including Alzheimer's disease, traumatic brain injury and seizure disorders."

Brain modularity is the theory that there are functionally specialized regions in the brain responsible for different, specific cognitive processes. For example, the frontal lobes of the human brain are involved in executive functions, such as reasoning and planning, while the fusiform face area located in the lower rear of the brain is involved in recognizing faces.

Reduced modularity, said George, likely interferes with "normal neuronal activity and information processing and contributes to cognitive impairment, emotional distress and intense craving observed in mice during abstinence from alcohol."

Due to the format of the testing, George said it was not clear if the reduced modularity was permanent. "So far, we only know that it lasts at least one week into abstinence. We have not tested longer durations of abstinence, but it's one of our goals."

George and colleagues used multiple new and emerging imaging technologies to create their whole-brain atlas of mouse brains, capable of being viewed at the level of single cells. The result was a first, they said, providing unprecedented data and insights.

"This new approach allows us to explore an entirely new universe. It can answer so many questions. What I am most interested in now is figuring out how early these brain changes start and how long do they last for. This would be critical to understanding when the switch to addiction happens and when does your brain come back to normal, if it ever does. We are also very interested in comparing the brain network of alcohol dependence with other drugs, such as cocaine, nicotine and methamphetamines."

The imaging approach cannot yet be used with human brains, which are far larger and more complex. "I don't think that it is possible to do it in humans now, the technology is just not there," said George. "But when I started doing this research 15 years ago, this technique didn't exist at all and I never ever imagined it would be possible, so who knows what the future will bring."

Reference: Kimbrough, A., Lurie, D. J., Collazo, A., Kreifeldt, M., Sidhu, H., Macedo, G. C., DEsposito, M., Contet, C., & George, O. (2020). Brain-wide functional architecture remodeling by alcohol dependence and abstinence. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1909915117

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How Alcohol Addiction and Abstinence Remodel the Brain - Technology Networks

Neuroscience

8-Year-Old Whiz Kid Teaches Neuroscience Online from Home – MENAFN.COM

(MENAFN - SomTribune) Amoy Antunet got hooked on science at the age of three after coming across a microscope owned by her father, who was a college student.

The young whiz kid from Atlanta, Georgia, soon became her father's 'study buddy.' Davin Shepherd, who was then 43, began explaining everything he was learning during his biology classes to his daughter.

Subsequently, the second-grader began experiments from a lab in her bedroom with a collection of test tubes, replica organs, microscopes, and chemicals she built for herself.

By the age of five, she had started appearing on the internet with her dad, conducting experiments and giving lessons from the lab.

'Donning a white lab coat, Amoy dissects mind-boggling topics including cell division, the heart, pH testing and her favorite the brain,' theDaily Mailwrote recently.

At the moment, her explainer videos on her Facebook page, Science For Children with Amoy Antunet, have over a million views.

Antunet, who also loves math and gymnastics, said she makes her videos because she wants to 'help people understand different types of science.'

'When I was a little girl I said I wanted to be a pharmacist but now I want to be a neurosurgeon who helps people with neurological disorders.

'So far I've mostly learnt about the heart and the brain and I want to learn about Multiple Sclerosis in the future so I can help sick people like my aunt, who has it.

'My daddy will teach me.'

Antunet with her dad. Photo: Daily Mail

Shepherd, who is proud of her daughter, said he will continue to help his talented daughter to achieve her goals.

'At first I thought it was cute but then I started seeing how she really grasped some of it,' he said.

'After a while it became something we did together. We would go through lessons and she would pretend to teach me, and that's how we learned.

'It's one of the things she does for playtime now. She will put on a lab coat and run to the lab and do all the stuff she wants.'

Amoy Antunet

Antunet, who was invited to the University of Alabama's Neuroscience Lab, has also appeared on CNN, the BBC and other major media outlets as well as conferences where she has spoken on Alzheimer's.

She was recently a keynote speaker at a Youth Innovation Summit that helps students get more interested in the STEAM and the STEM programs.

'If you scratch out the science stuff, I'm actually pretty normal,' the 8-year-old genius said while advising students at the summit this January: 'They should act on their potential, and if there's something that you really like you should act on it.'

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8-Year-Old Whiz Kid Teaches Neuroscience Online from Home - MENAFN.COM