Category Archives: Neuroscience

Alzheimers Alters COVID-19 Response in Olfactory Cells – Neuroscience News

Summary: Researchers uncovered how Alzheimers Disease (AD) impacts COVID-19 outcomes through changes in the olfactory mucosal cells. Their study focused on individuals with AD who experienced exacerbated COVID-19 symptoms.

Using an advanced 3D in vitro model of the olfactory mucosa, the research revealed that while initial infection rates were similar between healthy individuals and those with AD, the latter showed altered gene activities post-infection, indicating heightened oxidative stress and immune response changes.

This study provides crucial insights into the interplay between COVID-19 and AD, particularly through the olfactory system.

Key Facts:

Source: University of Eastern Finland

A new study identifies alterations in the transcriptomic signatures in human olfactory mucosal cells of individuals with Alzheimers disease following SARS-CoV-2 infection, potentially contributing to exacerbated COVID-19 outcomes.

The study was conducted at the University of Eastern Finland in collaboration with the University of Helsinki and published inJournal of Neuroinflammation.

The study was prompted by concerns about the impact of COVID-19 on individuals with pre-existing conditions such as Alzheimers disease (AD). Olfactory dysfunction, characterized by an impaired sense of smell, is commonly associated with COVID-19 and is also observed in persons with AD.

Exploring the olfactory mucosa as a direct interface between the external environment and the brain, the research aimed to investigate the interaction between SARS-CoV-2 infection and AD within the olfactory mucosa , assessing the potential for this tissue to serve as a plausible entry route for the virus into the brain.

Employing an innovative 3D in vitro model of the olfactory mucosa, the study utilized primary cells obtained from voluntary donors, including both cognitively healthy individuals and those diagnosed with AD.

These cells were cultivated at the air-liquid interface (ALI), a technique providing a controlled environment that closely mimics physiological conditions. The collection of olfactory mucosal biopsies was conducted collaboratively with Kuopio University Hospital.

This multidisciplinary research integrated expertise from molecular and cellular biology, neurology, and virology to investigate the effects of various SARS-CoV-2 variants on the olfactory mucosa.

Distinct immune responses after infection between AD patients and healthy individuals

Contrary to expectations, cells derived from healthy individuals and those with AD exhibited comparable susceptibility to infection by SARS-CoV-2 virus, indicating no significant difference in initial infection rates between the two groups.

However, a significant contrast emerged in the gene activity of infected cells from individuals with AD. Their cells displayed heightened oxidative stress, altered immune responses, and substantial changes in genes related to olfaction when compared to olfactory mucosal cells from cognitively healthy individuals.

The results suggest a plausible scenario where individuals affected by AD might face potentially more severe COVID-19 outcomes due to pre-existing inflammation in the olfactory mucosa, says Ali Shahbaz, a doctoral researcher in Professor Katja Kanninens research group at the University of Eastern Finland and the first author of the study.

The present study represents a pivotal advancement in understanding the intricate interplay between COVID-19 and AD.

Funding: The study was funded by the Academy of Finland.

Author: Ulla Kaltiala Source: University of Eastern Finland Contact: Ulla Kaltiala University of Eastern Finland Image: The image is credited to Neuroscience News

Original Research: Open access. Human-derived airliquid interface cultures decipher Alzheimers diseaseSARS-CoV-2 crosstalk in the olfactory mucosa by Katja Kanninen et al. Journal of Neuroinflammation

Abstract

Human-derived airliquid interface cultures decipher Alzheimers diseaseSARS-CoV-2 crosstalk in the olfactory mucosa

The neurological effects of the coronavirus disease of 2019 (COVID-19) raise concerns about potential long-term consequences, such as an increased risk of Alzheimers disease (AD). Neuroinflammation and other AD-associated pathologies are also suggested to increase the risk of serious SARS-CoV-2 infection. Anosmia is a common neurological symptom reported in COVID-19 and in early AD. The olfactory mucosa (OM) is important for the perception of smell and a proposed site of viral entry to the brain. However, little is known about SARS-CoV-2 infection at the OM of individuals with AD.

To address this gap, we established a 3D in vitro model of the OM from primary cells derived from cognitively healthy and AD individuals. We cultured the cells at the airliquid interface (ALI) to study SARS-CoV-2 infection under controlled experimental conditions. Primary OM cells in ALI expressed angiotensin-converting enzyme 2 (ACE-2), neuropilin-1 (NRP-1), and several other known SARS-CoV-2 receptor and were highly vulnerable to infection. Infection was determined by secreted viral RNA content and confirmed with SARS-CoV-2 nucleocapsid protein (NP) in the infected cells by immunocytochemistry. Differential responses of healthy and AD individuals-derived OM cells to SARS-CoV-2 were determined by RNA sequencing.

Results indicate that cells derived from cognitively healthy donors and individuals with AD do not differ in susceptibility to infection with the wild-type SARS-CoV-2 virus. However, transcriptomic signatures in cells from individuals with AD are highly distinct. Specifically, the cells from AD patients that were infected with the virus showed increased levels of oxidative stress, desensitized inflammation and immune responses, and alterations to genes associated with olfaction. These results imply that individuals with AD may be at a greater risk of experiencing severe outcomes from the infection, potentially driven by pre-existing neuroinflammation.

The study sheds light on the interplay between AD pathology and SARS-CoV-2 infection. Altered transcriptomic signatures in AD cells may contribute to unique symptoms and a more severe disease course, with a notable involvement of neuroinflammation. Furthermore, the research emphasizes the need for targeted interventions to enhance outcomes for AD patients with viral infection. The study is crucial to better comprehend the relationship between AD, COVID-19, and anosmia. It highlights the importance of ongoing research to develop more effective treatments for those at high risk of severe SARS-CoV-2 infection.

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Deep neural networks show promise as models of human hearing – Freethink

Computational models that mimic the structure and function of the human auditory system could help researchers design better hearing aids, cochlear implants, and brain-machine interfaces. A new study from MIT has found that modern computational models derived from machine learning are moving closer to this goal.

In the largest study yet of deep neural networks that have been trained to perform auditory tasks, the MIT team showed that most of these models generate internal representations that share properties of representations seen in the human brain when people are listening to the same sounds.

The study also offers insight into how to best train this type of model: The researchers found that models trained on auditory input including background noise more closely mimic the activation patterns of the human auditory cortex.

What sets this study apart is it is the most comprehensive comparison of these kinds of models to the auditory system so far. The study suggests that models that are derived from machine learning are a step in the right direction, and it gives us some clues as to what tends to make them better models of the brain, says Josh McDermott, an associate professor of brain and cognitive sciences at MIT, a member of MITs McGovern Institute for Brain Research and Center for Brains, Minds, and Machines, and the senior author of the study.

MIT graduate student Greta Tuckute and Jenelle Feather PhD 22 are the lead authors of the open-accesspaper, which appears today inPLOS Biology.

Deep neural networks are computational models that consists of many layers of information-processing units that can be trained on huge volumes of data to perform specific tasks. This type of model has become widely used in many applications, and neuroscientists have begun to explore the possibility that these systems can also be used to describe how the human brain performs certain tasks.

These models that are built with machine learning are able to mediate behaviors on a scale that really wasnt possible with previous types of models, and that has led to interest in whether or not the representations in the models might capture things that are happening in the brain, Tuckute says.

When a neural network is performing a task, its processing units generate activation patterns in response to each audio input it receives, such as a word or other type of sound. Those model representations of the input can be compared to the activation patterns seen in fMRI brain scans of people listening to the same input.

In 2018, McDermott and then-graduate student Alexander Kellreportedthat when they trained a neural network to perform auditory tasks (such as recognizing words from an audio signal), the internal representations generated by the model showed similarity to those seen in fMRI scans of people listening to the same sounds.

Since then, these types of models have become widely used, so McDermotts research group set out to evaluate a larger set of models, to see if the ability to approximate the neural representations seen in the human brain is a general trait of these models.

For this study, the researchers analyzed nine publicly available deep neural network models that had been trained to perform auditory tasks, and they also created 14 models of their own, based on two different architectures. Most of these models were trained to perform a single task recognizing words, identifying the speaker, recognizing environmental sounds, and identifying musical genre while two of them were trained to perform multiple tasks.

When the researchers presented these models with natural sounds that had been used as stimuli in human fMRI experiments, they found that the internal model representations tended to exhibit similarity with those generated by the human brain. The models whose representations were most similar to those seen in the brain were models that had been trained on more than one task and had been trained on auditory input that included background noise.

If you train models in noise, they give better brain predictions than if you dont, which is intuitively reasonable because a lot of real-world hearing involves hearing in noise, and thats plausibly something the auditory system is adapted to, Feather says.

The new study also supports the idea that the human auditory cortex has some degree of hierarchical organization, in which processing is divided into stages that support distinct computational functions. As in the 2018 study, the researchers found that representations generated in earlier stages of the model most closely resemble those seen in the primary auditory cortex, while representations generated in later model stages more closely resemble those generated in brain regions beyond the primary cortex.

Additionally, the researchers found that models that had been trained on different tasks were better at replicating different aspects of audition. For example, models trained on a speech-related task more closely resembled speech-selective areas.

Even though the model has seen the exact same training data and the architecture is the same, when you optimize for one particular task, you can see that it selectively explains specific tuning properties in the brain, Tuckute says.

McDermotts lab now plans to make use of their findings to try to develop models that are even more successful at reproducing human brain responses. In addition to helping scientists learn more about how the brain may be organized, such models could also be used to help develop better hearing aids, cochlear implants, and brain-machine interfaces.

A goal of our field is to end up with a computer model that can predict brain responses and behavior. We think that if we are successful in reaching that goal, it will open a lot of doors, McDermott says.

The research was funded by the National Institutes of Health, an Amazon Fellowship from the Science Hub, an International Doctoral Fellowship from the American Association of University Women, an MIT Friends of McGovern Institute Fellowship, a fellowship from theK. Lisa Yang Integrative Computational Neuroscience (ICoN) Center at MIT,and a Department of Energy Computational Science Graduate Fellowship.

Republished with permission ofMIT News. Read theoriginal article.

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Deep neural networks show promise as models of human hearing - Freethink

Integrating research and clinical care to uncover secrets of brain development – EurekAlert

image:

Large chains of migrating cells forming braided streams break down into a shower of young migrating neurons that continue to integrate into the entorhinal cortex and neighboring regions until 2-3 years of age.

Credit: Lab of Shawn Sorrell/Pitt

The human brain continues to be built after we are born for far longer than previously recognized, suggests research by Shawn Sorrells, assistant professor of neuroscience inthe Kenneth P. Dietrich School of Arts andSciences. Sorrellss research on postnatal brain development, published today inthe journalNature, shines light on fundamental processes that contribute to the development of important brain functions, such as learning, memory and spatial navigation.

The new research suggests that a subset of inhibitory neurons within the entorhinal cortex, or EC -- an area of the brain essential for forming memories -- continue to migrate into this region where they build new neuronal connections from birth through toddlerhood. The study suggests that extensive postnatal neuronal migration across the EC might underlie critical neuroplasticity periods during which the brain is especially receptive to changes and adaptations. The discovery also points to a possible reason why EC neurons are more susceptible to neurodegeneration, since other recent studies have found that this same type of neuron is impacted early in Alzheimers disease.

By analyzing brain samples that were provided, in part, by the epilepsy tissue bank at UPMC Childrens Hospital and the Neuropathology Department at UPMC Presbyterian Hospital, Sorrells' research team was first to show that, unlike what was previously thought, neuronal migration of such scale and duration is extensive within regions that control thoughts and emotions. The discovery offers an explanation for how the human brain makes billions of new neurons over a very short time span through a mechanism that allows neurons to continue arriving after birth.

It is generally thought that the brain is done recruiting neurons by the time an individual is born, said Sorrells. We were incredibly excited to learn that not only does large-scale neuronal migration continue into specific brain regions, but that this process also continues into ages when children are crawling and beginning to walk.

Imaging analysis

Human tissue samples

Protracted Neuronal Recruitment in the Temporal Lobe of Young Children

20-Dec-2023

A.A.B is a co-founder and is on the Scientific Advisory Board of Neurona Therapeutics. C.J.Y is a Scientific Advisory Board member for and holds equity in Related Sciences and ImmunAI, a consultant for and holds equity in Maze Therapeutics, and a consultant for TReX Bio. C.J.Y. has received research support from Chan Zuckerberg Initiative, Chan Zuckerberg Biohub, and Genentech

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Fanta and TikTok collaborate to challenge tastebuds with neuroscience experiment – Bizcommunity.com

Fanta has collaborated with TikTok to release the #FantaTikTokExperience an entertaining and innovative experience combining flavour, fun, and cutting-edge technology for TikTok Creators.

The adventure is rooted in fascinating neuroscientific findings that unravel how our senses may influence our perceptions of flavour. Could watching a TikTok video change the perception of the taste of a Fanta flavour? That's precisely what the Fanta set out to discover with this experiment.

"Through our innovative collaboration with TikTok, we have delved into intriguing new facets of sensory perception," says Zainab Mohamed, Fanta senior brand director at Coca-Cola Africa. "The compelling dynamics between our senses have never been more apparent. The power of visuals and sounds may transform the taste experience a revelation that adds a whole new layer of excitement to enjoying Fanta. With TikTok's pulsating platform, we have been able to bring this sensory adventure to life, providing an engaging, immersive, and truly unique experience for our influencers."

To test this phenomenon, TikTok Creators were invited to scan a QR code on limited-edition Fanta cans. Fanta launched a WebAR platform, guiding users through TikTok videos which the creators watched while consuming a limited-edition Fanta beverage, offering a fun and interactive experience. As the creators sipped their Fanta beverage, they were presented with the opportunity to test if they could sense the flavour shifting from fruity to tangy, or even bitter, based on the video they watched.

Prolonging the thrill, an unforgettable live spectacle was hosted at Cape Town's Zeitz MOCAA on 20 December 2023. It took the neuroscientific experiment a step further by serving influencers the limited-edition Fanta beverage, set against a backdrop of distinct sounds and eye-catching visuals.

The event also featured "Reaction Booths", fitted with cameras to record the spontaneous responses of creators as they viewed TikTok videos while savoring the #FantaTikTokExperience. The #FantaTikTokExperience is a testament to Fanta's commitment to providing unique, creative and playful experiences to their audiences. This unique blend of technology, creativity, and sensory exploration breaks new ground, adding a playful twist to enjoying Fanta.

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Fanta and TikTok collaborate to challenge tastebuds with neuroscience experiment - Bizcommunity.com

DeepSouth Supercomputer: Revolutionizing Our Understanding of the Brain – Medriva

Revolutionizing Our Understanding of the Brain

In a significant technological breakthrough, a supercomputer capable of simulating the entire human brain is set to be switched on in 2024. This incredible innovation, named the DeepSouth supercomputer, is expected to revolutionize our understanding of the brain and its functions. The project, spearheaded by Western Sydney University, aims to create a digital replica of the human brain, providing researchers with a groundbreaking tool to study neurological disorders and develop new treatments.

The DeepSouth supercomputer uses a neuromorphic system that emulates biological processes, simulating large networks of spiking neurons at 228 trillion synaptic operations per second. This remarkable system is purpose-built to operate like networks of neurons, requiring less power and enabling greater efficiencies. The supercomputer, to be based at Western Sydney University, is expected to be operational by April 2024.

The implications and potential applications of this technology are vast. It is anticipated that this supercomputer will significantly advance smart devices, sensors for manufacturing and agriculture, and smarter AI applications. Furthermore, the DeepSouth supercomputer will allow researchers to better understand how brains can process massive amounts of information using such little power. This knowledge could potentially lead to the creation of a cyborg brain vastly more powerful than our own, revolutionizing our understanding of how our brains work.

The development of the worlds first human brain-scale supercomputer is considered a game changer for the study of neuroscience. There is widespread interest from researchers studying neuroscience and those who want to prototype new engineering solutions in the AI space. If successful, this project could lead to significant advancements in neuroscience and medical technology, marking a major milestone in the fields of neuroscience and artificial intelligence.

In conclusion, the DeepSouth supercomputer represents a significant leap in our quest to understand and replicate the complex workings of the human brain. The potential benefits of this technology range from a deeper understanding of neurological disorders to advancements in AI applications. As we eagerly await the launch of this supercomputer in 2024, we can only imagine the wealth of insights and breakthroughs that lie ahead in the field of neuroscience and beyond.

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DeepSouth Supercomputer: Revolutionizing Our Understanding of the Brain - Medriva

Revolution in Neuroscience: Wireless Neuron Communication – BNN Breaking

Wireless Communication Between Neurons: A Game-Changer in Neuroscience

In a breakthrough for neuroscience research, scientists have uncovered a novel form of communication between neurons a wireless, or non-synaptic, mode of interaction. This revolutionary discovery challenges the traditional understanding of synaptic communication, where neurons connect via axons and dendrites with neurotransmitters bridging a minuscule gap between them. Synaptic communication, akin to a wired internet connection, maintains a degree of privacy, while this newfound wireless communication allows chemical messengers to traverse more extended distances through the intercellular space, potentially risking message interception.

Contributing significantly to our comprehension of neural communication is the nematode Caenorhabditis elegans (C. elegans). Possessing just over 300 neurons, C. elegans has been fundamental in mapping the connections between neurons, known as the connectome. The first comprehensive connectome was published back in 1986, and most recently, researchers have published an inventory of all wireless connections within C. elegans, particularly those utilizing neuropeptides as chemical messengers.

One research group predicted the wireless connection map based on gene expression within neurons, while another employed optogenetics to examine the impact of activating or deactivating nerve cells on their neighboring cells. These findings suggest a profound departure of the wireless communication network from the synaptic network, underscoring the complexity of the neural communication matrix.

The implications of these findings are far-reaching. They offer a fresh perspective on the functioning of the human nervous system and how diseases or medications might influence it, potentially revolutionizing treatments for neurological disorders and the design of brain-computer interfaces (BCIs). BCIs, systems that enable direct communication between the brain and an external device or computer system, have immense potential in medicine, rehabilitation, and human augmentation. BCIs harness the power of real-time recordings of brain activity for communication and control, allowing individuals to interact with devices using only their thoughts.

Future applications of this research could include the treatment of neurological diseases such as Attention Deficit Hyperactivity Disorder (ADHD), ALS, epilepsy, and stroke, as well as advancements in functional brain mapping and consciousness assessment. As we continue to unravel the mysteries of the brain and its complex communication networks, the possibilities seem endless.

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Revolution in Neuroscience: Wireless Neuron Communication - BNN Breaking

AI’s memory-forming mechanism found to be strikingly similar to that of the brain – EurekAlert

image:

(a) Diagram illustrating the ion channel activity in post-synaptic neurons. AMPA receptors are involved in the activation of post-synaptic neurons, while NMDA receptors are blocked by magnesium ions (Mg) but induce synaptic plasticity through the influx of calcium ions (Ca) when the post-synaptic neuron is sufficiently activated. (b) Flow diagram representing the computational process within the Transformer AI model. Information is processed sequentially through stages such as feed-forward layers, layer normalization, and self-attention layers. The graph depicting the current-voltage relationship of the NMDA receptors is very similar to the nonlinearity of the feed-forward layer. The input-output graph, based on the concentration of magnesium (), shows the changes in the nonlinearity of the NMDA receptors.

Credit: Institute for Basic Science

An interdisciplinary team consisting of researchers from the Center for Cognition and Sociality and the Data Science Group within the Institute for Basic Science (IBS) revealed a striking similarity between the memory processing of artificial intelligence (AI) models and the hippocampus of the human brain. This new finding provides a novel perspective on memory consolidation, which is a process that transforms short-term memories into long-term ones, in AI systems.

In the race towards developing Artificial General Intelligence (AGI), with influential entities like OpenAI and Google DeepMind leading the way, understanding and replicating human-like intelligence has become an important research interest. Central to these technological advancements is the Transformer model [Figure 1], whose fundamental principles are now being explored in new depth.

The key to powerful AI systems is grasping how they learn and remember information. The team applied principles of human brain learning, specifically concentrating on memory consolidation through the NMDA receptor in the hippocampus, to AI models.

The NMDA receptor is like a smart door in your brain that facilitates learning and memory formation. When a brain chemical called glutamate is present, the nerve cell undergoes excitation. On the other hand, a magnesium ion acts as a small gatekeeper blocking the door. Only when this ionic gatekeeper steps aside, substances are allowed to flow into the cell. This is the process that allows the brain to create and keep memories, and the gatekeeper's (the magnesium ion) role in the whole process is quite specific.

The team made a fascinating discovery: the Transformer model seems to use a gatekeeping process similar to the brain's NMDA receptor [see Figure 1]. This revelation led the researchers to investigate if the Transformer's memory consolidation can be controlled by a mechanism similar to the NMDA receptor's gating process.

In the animal brain, a low magnesium level is known to weaken memory function. The researchers found that long-term memory in Transformer can be improved by mimicking the NMDA receptor. Just like in the brain, where changing magnesium levels affect memory strength, tweaking the Transformer's parameters to reflect the gating action of the NMDA receptor led to enhanced memory in the AI model. This breakthrough finding suggests that how AI models learn can be explained with established knowledge in neuroscience.

C. Justin LEE, who is a neuroscientist director at the institute, said, This research makes a crucial step in advancing AI and neuroscience. It allows us to delve deeper into the brain's operating principles and develop more advanced AI systems based on these insights.

CHA Meeyoung, who is a data scientist in the team and at KAIST, notes, The human brain is remarkable in how it operates with minimal energy, unlike the large AI models that need immense resources. Our work opens up new possibilities for low-cost, high-performance AI systems that learn and remember information like humans.

What sets this study apart is its initiative to incorporate brain-inspired nonlinearity into an AI construct, signifying a significant advancement in simulating human-like memory consolidation. The convergence of human cognitive mechanisms and AI design not only holds promise for creating low-cost, high-performance AI systems but also provides valuable insights into the workings of the brain through AI models.

Experimental study

Not applicable

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Navigating the neuroscientific landscape with Dr Judy Illes – Drug Target Review

In a world grappling with the growing spectre of eco-anxiety and the pressing challenges posed by climate change, Dr Judy Illes, a distinguished figure in the field of neuroscience, sheds light on the role neuroscientists play in contributing to the discourse on environmental issues and their profound impact on individual and collective well-being. In this interview, Judy emphasises the need for evidence-based neuroscience to address the mental health implications of environmental changes, urging a departure from geographical silos to foster global collaboration. The discussion extends to strategies for disseminating neuroscientific research across diverse cultural landscapes and the practical implications of bridging the gap between research and public awareness.

I dont think it is a question of neuroscientists having to shoulder the responsibility of responding to and addressing questions of eco-anxiety, climate change, and environmental change, but rather a matter of upping the interest in this space and delivering more evidence through great research. We need more good neuroscience discovery and meaningful clinical translation to address the issues that were seeing and that are being debated. On the mental health side, there is anxiety around climate change Eco-Anxiety. On the neurologic side, there are findings about neurotoxins and environmental contaminants showing correlations with a variety of neurologic diseases across the lifespan from children to adults. Good study design, solid evidence, and good information dissemination with explicit evidence-based mitigation of misinformation will really contribute to climate change and environmental decision-making, policymaking, and improvements in brain-related health systems and care.

That is such an important question and it speaks directly to the global movement in neuroscience today. Global neuroscience cross-national, cross-geographic collaboration is so important to bring the kind of evidence about which I spoke in response to your first question. There is no point in addressing climate change, environmental change, contaminants from neurotoxins and so on in geographic silos. These affect all people across all nations. We have so much to learn from each other. We have different perspectives, different languages, and potentially different belief systems. When we combine these into an integrated, concerted collaborative program, we will be able to advance the kind of neuroscience that I hope that my lecture at the Society for Neuroscience inspired and also help to propel forward the work of the International Brain Initiative whose headquarters reside with me now in Canada. This is precisely what were trying to achieve: geopolitically conscious, border-free global cooperation in neuroscience.

This question is a good segue from the previous one. Thank you. First, let me say that I am a person of European background and I have had the privilege and the honour of working with indigenous peoples across Canada to learn about indigenous ways of knowing, of knowledge, of methods. My team has done empirical work through systematic literature reviews, scoping reviews, and a variety of research collaborations with indigenous Canadian people. I am also currently working around questions about portable MRI, for example, with colleagues across the USA, led by the University of Minnesota, to understand the important relationships and ethical considerations that come into play when were talking about work, research, and clinical translation that has to do with expanded access to MRI scanning with people from multiple cultures, and many who are in rural and remote regions of North America and the world.

With that preamble, to respond, I respectfully refer to Elder Albert Marshall and to what he called two-eyed seeing, which is a powerful way to bring together traditional belief systems, rooted in the medicine wheel, holism, relationships with the land and the earth, sky, water, air and fire, with biomedical explanations of mental health and neurologic disease. On the neuroscience side, we think about cells to systems: genes, brain development, demyelination, degeneration. It is equally meaningful to integrate this thinking with learnings and knowledge that preceded our understanding about genes and neuroanatomy and neurophysiology. In the past, we to dismissed traditional forms of belief systems. Today, we are seeing through the work of people in neuroscience, health sciences, ethics and law, anthropology and sociology that coupling the two can really bring wellness to an understanding of some of the major burdens of brain and mental health that affect people and societies today.

Again, a wonderful question, Taylor. So there are innumerable strategies. I will only mention three that immediately come to mind.

The first is about data and evidence. Evidence, good science, and design that takes into account not only Western approaches but approaches from different people of different backgrounds and ways of knowing and doing that might date back to time immemorial. That is number one: data, and irrefutable evidence that are respectful of all methods of doing.

The second is working collaboratively in a very engaged way with people of different cultures and different geographies, whether they are Elders from communities or whether they are neuroscientists from different communities and geographic locations. In this way, the maximum breadth and potential of neuroscience discovery will be realised.

The third is collaboration among people who have expertise in the ethics of communication and dissemination of results, or with science communicators to maximize not only what results or findings are disseminated but how they are disseminated. That takes the form of K-12 teaching, undergraduate teaching, graduate teaching, postdoctoral teaching, teaching and communicating throughout the academic ranks, and equally importantly, through public outreach. I think what weve seen over the past 25 years of neuroethics is a tremendous improvement in the way that science reporting is taking place around brain and mind around neuroscience. There really is a commitment, I believe, to working in a far more reciprocal way between the communication side and the science side to ensure that what gets out there is meaningful and appropriately-tailored to distinct audiences. It is multi-layered. It starts well before data collection, at the design and planning phases of research, and then all the way through engaging with the public as I mentioned, and with students of all ages.

I think the responsible way to answer your question is to speak to the importance of systematic neuroscience discovery and systematic engagement. A very small study pharmacologic, behavioral, whatever that is robust can have a huge impact on changing the way health and policymakers think about an aspect of climate change, or a neurotoxin. For example, in my lecture, I spoke about glyphosates. I talked about methylmercury. Neuroscientists could not possibly take on the whole scope of neurotoxic contaminants for a research platform. The challenge is to choose one, choose an important one, and help decode and disentangle why there seems to be still controversies and debates around harms versus benefits that are leading to heterogeneous and conflicting international policies. Solve critical questions for one neurotoxin. Then move on to the next.

I talked a lot about fracking and how data show that the pushing hydrochloric acid into the earth to create fissures not great for the environment, for keeping the land and water clean, or for ensuring that traditional relationships with the land are preserved. The risk of fracking have to be taken in balance though with the economic benefits to communities that dont have a lot of resources, for example, and may even be faced with food and water security. We must look at harms and benefits always, always in balance. We have to take these problems and tackle them bit by bit. Climate change, too big as a whole. But finding ways to protect children with severe brain disorders such as epilepsy whose condition might be exacerbated by extreme heat that can be tackled. Environmental change with respect to neurotoxins too big. Discovering and addressing differential proximate and epigenetic effects of different neurotoxins that can be tackled.

Neuroscience requires patience and systematic, rigorous deliberate methods. Today there is a new openness to thinking about all aspects of what results may suggest and how they may inform how people behave, govern, and invest in each other going forward.

About the author

Dr Judy Illes, CM, PhD, FCAHS, FRSC

University of British Columbia (UBC)

Dr Judy Illes is Professor of Neurology at the University of British Columbia (UBC),Distinguished University Scholar, UBC Distinguished Scholar in Neuroethics, and Director of Neuroethics Canada. She is a pioneer of the field of neuroethics through which she has made groundbreaking contributions to cross-cultural ethical, legal, social and policy challenges at the intersection of the brain sciences and biomedical ethics. Among her many commitments, she is Chair of the International Brain Initiative and co-Lead of the IBIs Canadian Brain Research Strategy. She serves as Director-at-Large of the Canadian Academy of Health Sciences,and is a member of the Ethics, Law and Humanities Committee of the American Academy of Neurology.

Dr Illes is the immediate past Vice Chair of the Advisory Board of the Institute for Neuroscience, Mental Health and Addiction of the Canadian Institutes of Health Research (CIHR), and of CIHRs Standing Committee on Ethics.Her recent books, a series calledDevelopments in Neuroethics and Bioethics, focus on pain, global mental health, neurotechnology, transnational laws, environmental neuroethics, neurodevelopment, and neuroAI. Dr Illes was awarded the Order of Canada, the countrys highest recognition of its citizens, in 2017.

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Navigating the neuroscientific landscape with Dr Judy Illes - Drug Target Review

Metabolic Markers of Depression Identified – Neuroscience News

Summary: Researchers revealed a crucial link between cellular metabolism and major depressive disorder, particularly in treatment-refractory cases and suicidal ideation. This research found specific blood metabolites that differ in people with depression, providing new biomarkers for risk assessment.

The study also highlights sex-based differences in depressions metabolic impact and suggests that mitochondrial dysfunction plays a role in suicidal ideation. These insights offer new avenues for personalized treatment and prevention strategies, potentially utilizing supplements like folate and carnitine to address metabolic gaps.

Key Facts:

Source: UCSD

Major depressive disorder affects 16.1 million adults in the United States and costs $210 billion annually. While the primary symptoms of depression are psychological, scientists and doctors have come to understand that depression is a complex disease with physical effects throughout the body.

For example, measuring markers of cellular metabolism has become an important approach to studying mental illnesses and developing new ways to diagnose, treat and prevent them.

Researchers at University of California San Diego School of Medicine have now advanced this line of work in a new study, revealing a connection between cellular metabolism and depression.

They found that people with depression and suicidal ideation had detectable compounds in their blood that could help identify individuals at higher risk of becoming suicidal. The researchers also found sex-based differences in how depression impacts cell metabolism.

The findings, published December 15, 2023 inTranslational Psychiatry, could help personalize mental health care and potentially identify new targets for future drugs.

Mental illnesses like depression have impacts and drivers well beyond the brain, saidRobert Naviaux, MD, PhD, a professor in the Department of Medicine, Pediatrics and Pathology at UC San Diego School of Medicine.

Prior to about ten years ago it was difficult to study how the chemistry of the whole body influences our behavior and state of mind, but modern technologies like metabolomics are helping us listen in on cells conversations in their native tongue, which is biochemistry.

While many people with depression experience improvement with psychotherapy and medication, some peoples depression is treatment-refractory, meaning treatment has little to no impact. Suicidal thoughts are experienced by the majority of patients with treatment-refractory depression, and as many as 30% will attempt suicide at least once in their lifetime.

Were seeing a significant rise in midlife mortality in the United States, and increased suicide incidence is one of many things driving that trend, said Naviaux. Tools that could help us stratify people based on their risk of becoming suicidal could help us save lives.

The researchers analyzed the blood of 99 study participants with treatment-refractory depression and suicidal ideation, as well as an equal number of healthy controls.

Among the hundreds of different biochemicals circulating in the blood of these individuals, they found that five could be used as a biomarker to classify patients with treatment-refractory depression and suicidal ideation. However, which five could be used differed between men and women.

If we have 100 people who either dont have depression or who have depression and suicidal ideation, we would be able to correctly identify 85-90 of those at greatest risk based on five metabolites in males and another 5 metabolites in females, said Naviaux.

This could be important in terms of diagnostics, but it also opens up a broader conversation in the field about whats actually leading to these metabolic changes.

While there were clear differences in blood metabolism between males and females, some metabolic markers of suicidal ideation were consistent across both sexes. This included biomarkers for mitochondrial dysfunction, which occurs when the energy-producing structures of our cells malfunction.

Mitochondria are some of the most important structures of our cells and changed mitochondrial functions occur in a host of human diseases, added Naviaux.

Mitochondria produce ATP, the primary energy currency of all cells. ATP is also an important molecule for cell-to-cell communication, and the researchers hypothesize it is this function that is most dysregulated in people with suicidal ideation.

When ATP is inside the cell it acts like an energy source, but outside the cell it is a danger signal that activates dozens of protective pathways in response to some environmental stressor, said Naviaux.

We hypothesize that suicide attempts may actually be part of a larger physiological impulse to stop a stress response that has become unbearable at the cellular level.

Because some of the metabolic deficiencies identified in the study were in compounds that are available as supplements, such as folate and carnitine, the researchers are interested in exploring the possibility of individualizing depression treatment with these compounds to help fill in the gaps in metabolism that are needed for recovery. Naviaux hastens to add that these supplements are not cures.

None of these metabolites are a magic bullet that will completely reverse somebodys depression, said Naviaux.

However, our results tell us that there may be things we can do to nudge the metabolism in the right direction to help patients respond better to treatment, and in the context of suicide, this could be just enough to prevent people from crossing that threshold.

In addition to suggesting a new approach to personalize medicine for depression, the research could help scientists discover new drugs that can target mitochondrial dysfunction, which could have wide implications for human health in general.

Many chronic diseases are comorbid with depression, because it can be extremely stressful to deal with an illness for years at a time, said Naviaux.

If we can find ways to treat depression and suicidal ideation on a metabolic level, we may also help improve outcomes for the many diseases that lead to depression.

Many chronic illnesses, such as post-traumatic stress disorder and chronic fatigue syndrome, are not lethal themselves unless they lead to suicidal thoughts and actions. If metabolomics can be used to identify the people at greatest risk, it could ultimately help us save more lives.

Co-authors include: Jane C. Naviaux, Lin Wang, Kefeng Li, Jonathan M. Monk and Sai Sachin Lingampelly at UC San Diego, Lisa A. Pan, Anna Maria Segreti, Kaitlyn Bloom, Jerry Vockley, David N. Finegold and David G. Peters at University of Pittsburgh School of Medicine, and Mark A. Tarnopolsky at McMaster University.

Author: Miles Martin Source: UCSD Contact: Miles Martin UCSD Image: The image is credited to Neuroscience News

Original Research: Open access. Metabolic features of treatment-refractory major depressive disorder with suicidal ideation by Robert Naviaux et al. Translational Psychiatry

Abstract

Metabolic features of treatment-refractory major depressive disorder with suicidal ideation

Peripheral blood metabolomics was used to gain chemical insight into the biology of treatment-refractory Major Depressive Disorder with suicidal ideation, and to identify individualized differences for personalized care.

The study cohort consisted of 99 patients with treatment-refractory major depressive disorder and suicidal ideation (trMDD-SIn=52 females and 47 males) and 94 age- and sex-matched healthy controls (n=48 females and 46 males). The median age was 29 years (IQR 2242). Targeted, broad-spectrum metabolomics measured 448 metabolites. Fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) were measured as biomarkers of mitochondrial dysfunction.

The diagnostic accuracy of plasma metabolomics was over 90% (95%CI: 0.801.0) by area under the receiver operator characteristic (AUROC) curve analysis. Over 55% of the metabolic impact in males and 75% in females came from abnormalities in lipids.

Modified purines and pyrimidines from tRNA, rRNA, and mRNA turnover were increased in the trMDD-SI group. FGF21 was increased in both males and females. Increased lactate, glutamate, and saccharopine, and decreased cystine provided evidence of reductive stress. Seventy-five percent of the metabolomic abnormalities found were individualized.

Personalized deficiencies in CoQ10, flavin adenine dinucleotide (FAD), citrulline, lutein, carnitine, or folate were found. Pathways regulated by mitochondrial function dominated the metabolic signature.

Peripheral blood metabolomics identified mitochondrial dysfunction and reductive stress as common denominators in suicidal ideation associated with treatment-refractory major depressive disorder.

Individualized metabolic differences were found that may help with personalized management.

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Metabolic Markers of Depression Identified - Neuroscience News

URI’s new neuro-learning center to boost brain education – EurekAlert

image:

A young study participant wears a functional Near Infrared Spectroscopy system cap, which allows neuro scientists to measure brain activity by monitoring changes in blood flow in the brain.

Credit: Submitted Photo

University of Rhode Island students and faculty members in multiple health disciplines will soon have access to state-of-the-art neuroscientific technology to enhance classroom lessons and research education, thanks to a grant from the Champlin Foundation.

College of Health Sciences Professors Mariusz Furmanek and Alisa Baron, along with collaborators Mark Hartman, Nicole Logan, Ellen McGough and Kunal Mankodiya, will establish a Neuro-Learning Center that includes some of the most cutting-edge equipment available to neuroscientific researchers, allowing for the non-invasive study of relationships between brain activity and behavior, functional brain mapping, and mechanisms of neuroplasticity. The equipment will be available to undergraduate and graduate students as well as faculty in such disciplines as communicative disorders, physical therapy, kinesiology and biomedical engineering.

We are planning to establish the Neuro-Learning Center, which will allow that interdisciplinary interaction with faculty members from different departments, Furmanek said. In the majority of institutions, these are only used for research. Primarily, we would use them for education. There is, of course, a research component with this equipment, but the primary goal is to educate our students in neuroscience and knowledge about the brain.

The non-invasive technology includes a Transcranial Magnetic Stimulation system, which uses low-intensity magnetic stimulation to facilitate or inhibit neural activity in areas of the brain; and a functional Near Infrared Spectroscopy system (fNIRS), which is an advanced neuroimaging technique used to measure brain activity by monitoring changes in blood flow in the brain. The TMS is used in conjunction with a NeuroNavigation System to target specific areas of the brain for neurostimulation. Basically, the technology will allow students to look at specific areas of the brain and determine which areas of the brain are active and which should be stimulated.

Its a cap thats put on the head and it can be configured in any way depending on the part of the brain you want to look at, Baron said of the fNIRS system. You put the sources and detectors in the areas you are interested in on the scalp, and when a participant does a particular task, you can analyze the data to see what part of the brain lights upthe part of the brain that has more blood circulating to it. That shows the part of the brain that is the most active in trying to process that information from whatever task youre asking the participant to do. This is a non-invasive system thats used across the lifespan, which is a big benefit since a lot of people think of an MRI when thinking about neuroimaging techniques, having to put people into a scanner thats quite loud and not child friendly.

The systems are essential to study, diagnose and treat neurological diseases, such as depression, Alzheimers, Parkinsons, stroke and more. Both systems can be used together by multiple clinicians. For example, the fNIRS system can identify parts of the brain that have died or have decreased function due to a stroke. Physical therapists can then use the TMS system to apply stimulation to those parts of the brain. If needed, a neurosurgeon would use the NeuroNavigation system to improve precision and safety of surgery, then a speech language pathologist could use fNIRS again to examine the post-procedure brain activity and its impact on communication.

Such a collaborative and interdisciplinary approach will be emphasized when teaching our students to ensure the patients comprehensive care and recovery, the professors wrote in their funding proposal. There have been rapid advancements in the neuroscience field, including the types of equipment used. University courses and the training they provide must simultaneously evolve to ensure students are familiar with the techniques and technologies that will be utilized during their careers in patient care and research.

Having the advanced equipment available to undergraduate students will be unique to URI. Furmanek and Baron are unaware of any other institutions that have the equipment for training undergraduate students and early-career graduate students, despite their widespread use by researchers and clinicians in the field. As important as the research capabilities is the educational component for students seeking careers in multiple health disciplines.

The huge benefit to these systems is their portability. We can actually take them into the classroom so students can see how to use it, how to put it on someone, how to analyze the data, all in the classroom without having to pull them out of the class into the lab, Baron said. A lot of these technologies are only available in laboratory spaces, which creates a lot of inequity for students. Were getting students access to these technologies early so they can understand and get comfortable using them, so thats one more marketable skill when they go on the job market.

Baron and Furmanek expect to begin acquiring the advanced technology in the spring, and expect to have it available for classroom use by fall 2024. The Neuro-Learning Center and the equipment will be housed between Furmaneks and Barons labs in Independence Square on the Kingston campus.

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URI's new neuro-learning center to boost brain education - EurekAlert