Category Archives: Neuroscience

Summary: In a first-of-its-kind study, researchers developed an electronic implant that collected information about brain activity from a single neuron for over one year.

Source: Harvard

When a person experiences a happy or sad mood, which brain cells are active?

To answer that question, scientists need to understand how individual brain cells contribute to a larger network of brain activity and what role each cell plays in shaping behavior and overall health. Until now, its been difficult to get a clear view of howbrain cellsin living animals behave over extended periods of time.

But Jia Lius group at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) has developed an electronic implant that collected detailed information about brain activity from a single cell of interest for more than a year.

Their findings, based on research in mice, are reported inNature Neuroscience.

This research solves a fundamental issuethe challenge of creating a brain-electronic interface that does not disturbbrain functionor degrade over time, says Liu, who is an assistant professor of bioengineering at SEAS, where he leads a lab dedicated to bioelectronics.

Neuroscientists have long sought better tools to study different cells in the brain, including neurons (which transmit electrical and chemical messages) and microglia (immune cells responsible for maintaining brain health).

A single neuron is very smallonly 10 to 100 micrometersand when it fires, its action potential (the spike inelectrical activity) only lasts about two milliseconds, Liu says.

Certain techniques can detect brain activity from specific cells of interest for short-lived experiments in small areas of the brain, either in tissue recently removed from animals or by using probes or optogenetic techniques to capture activity in situ.

But these conditions are not true to life and they dont provide detailed enough information about electrical activity in individual cells to understand how activity changes with age and otherlife experiences, Liu says. Behaviors, memories, and disease all build up over the course of days, weeks, months, and years.

Much of the difficulty to date, he says, has been due to a mismatch in mechanical properties between livingbrain tissueand electronic recording devices. This has prevented long-term, precise recording of how neurons and microglia behave over time.

The brain is very soft, like the texture of tofu or pudding. In contrast, electronics are rigid. Any small movement of the brain can cause conventional sensors to drift and move in living brain tissue. That mismatch in structure can cause cells around the implantation site to degrade.

To circumvent the problem, Lius team, which specializes in engineering nanoelectronics or cyborgs to bridge the gap between living tissue and electronics, developed an implantable device and minimally invasive technique for delivering it safely into the brain.

The mesh-like, flexible nanoelectronic sensor is designed to be inserted into brain tissue using a water-soluble polymer shuttle. Prior to implantation, the device and its delivery shuttle are connected lithographically. Once the implant is in the brain, a simple saline solution is applied to dissolve the shuttle, leaving only the mesh electronic sensor behind.

In mouse studies, when Lius team implanted their nanoelectronic sensors into multiple areas of the brain, the implantation process and presence of the sensors resulted in minimal disturbance to brain tissue. Then, targeting single neurons for analysis, they used the devices to record the electrical activity of those same cells over the course of the mices adult lives.

Even after one year, we didnt see any degradation of the individual neurons or proliferation of the microglia we were interested in recording with the devices, Liu says. Theres no other technology out there that can track single-cellaction potentialfrom the same cells in active animals over the course of a few months and a year.

Looking ahead, Liu plans to further develop the technique so thatbrain activitycan be transmitted in real time from the biological neural network to an artificial neural network in a computer for analysis. And, he wants to explore how the mesh nanoelectronic sensors can be used to study phenomena such as neural representation.

When you watch a movie or see a car drive down the road, your brain generates electrical activity to represent those images, he says. During that process of neural representation, the brain encodes sensory information and thoughts into a model of external stimuli.

Liu says that, for example, moods are influenced byneural representation, and hes especially interested in studying how changes of neural representations and brain states impact mood fluctuations over time.

Maybe one day its cold and gray outside, and you feel unhappy and in a bad mood. Another day, its sunny and youre on the beach and youre in a great mood. How those representations change in the brain cannot be studied by current technology because we havent been able to stably track activity from the same neuron, he says. This research completely overcomes that limitation. Its the beginning of a new era of neuroscience.

An ultimate goal of Lius research is to develop diagnostic and therapeutic methods for neurological, cardiovascular and developmental diseases.

Author: Kat J. McAlpineSource: HarvardContact: Kat J. McAlpine HarvardImage: The image is credited to Liu Lab, Harvard SEAS

Original Research: Closed access.Tracking neural activity from the same cells during the entire adult life of mice by Siyuan Zhao et al. Nature Neuroscience

Abstract

Tracking neural activity from the same cells during the entire adult life of mice

Stably recording the electrical activity of the same neurons over the adult life of an animal is important to neuroscience research and biomedical applications. Current implantable devices cannot provide stable recording on this timescale.

Here, we introduce a method to precisely implant electronics with an open, unfolded mesh structure across multiple brain regions in the mouse.

The open mesh structure forms a stable interwoven structure with the neural network, preventing probe drifting and showing no immune response and neuron loss during the year-long implantation.

Rigorous statistical analysis, visual stimulus-dependent measurement and unbiased, machine-learning-based analysis demonstrated that single-unit action potentials have been recorded from the same neurons of behaving mice in a very long-term stable manner.

Leveraging this stable structure, we demonstrated that the same neurons can be recorded over the entire adult life of the mouse, revealing the aging-associated evolution of single-neuron activities.

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Trained Brains Rapidly Suppress Visual Distractions – Neuroscience News

February 26, 2023 medical

Summary: Following training, the brains visual center can suppress neuronal responses to pop-out distractors that are usually enhanced compared to other, non-distracting stimuli.

Source: KNAW

Have you ever found yourself searching for your keys or phone only to end up getting distracted by a brightly colored object that grabs your attention?

This type of attentional capture by objects that stand out from their surroundings is known as pop-out. Pop-out is often functional, for instance when we want people to pay attention to bright red road signs. It can however also distract us from our goals, for instance when a brightly colored binder prevents us from finding our keys on a cluttered desk.

Would it not be nice if pop-out for distracting items could somehow be blocked or suppressed to avoid distractions and help us find whatever we are looking for faster?

New research from the Vision and Cognition group at the Netherlands Institute for Neuroscience, published in PNAS, demonstrates that this is indeed possible. After training, the visual brain can suppress neuronal responses to pop-out distractors that are usually enhanced compared to responses to other, non-distracting, items.

The researchers trained monkeys to play a video game in which they searched for a unique shape among multiple items, while a uniquely colored item tried to distract them. As soon as the monkeys found the unique shape, they made an eye movement to it to indicate their choice.

After some training, monkeys became very good at this game and almost never made eye movements to the distractor.

Neurons in area V4 of the visual cortex, a brain area that processes visual information relatively early after is is captured by the eyes, showed consistently enhanced responses to the shape target stimuli.

Responses to the distracting color stimuli on the other hand were only very briefly enhanced but became rapidly suppressed. It appears that the brain first briefly detects the presence of the distracting stimulus, and then quickly suppresses it to avoid that it will interfere with the search for the shape target.

The color pop-out signal that might cause distraction is thus essentially inverted into a kind of negative pop-out, or pop-in, to avoids distraction.

Researcher Chris Klink: Choosing what to attend to is very important for visual perception, and behavior in general. Even though the brain has impressive processing power, it simply cannot handle all available information at once. Attention needs to strike a balance between our own internally generated goals and whatever appears to be important in the environment.

Dealing with distraction in an efficient way is a crucial aspect of that process, that we now understand a little bit better.

Author: Eline FeenstraSource: KNAWContact: Eline Feenstra KNAWImage: The image is in the public domain

Original Research: Closed access.Inversion of pop-out for a distracting feature dimension in monkey visual cortex by Chris Klink et al. PNAS

Abstract

Inversion of pop-out for a distracting feature dimension in monkey visual cortex

During visual search, it is important to reduce the interference of distracting objects in the scene. The neuronal responses elicited by the search target stimulus are typically enhanced. However, it is equally important to suppress the representations of distracting stimuli, especially if they are salient and capture attention.

We trained monkeys to make an eye movement to a unique pop-out shape stimulus among an array of distracting stimuli.

One of these distractors had a salient color that varied across trials and differed from the color of the other stimuli, causing it to also pop-out. The monkeys were able to select the pop-out shape target with high accuracy and actively avoided the pop-out color distractor.

This behavioral pattern was reflected in the activity of neurons in area V4. Responses to the shape targets were enhanced, while the activity evoked by the pop-out color distractor was only briefly enhanced, directly followed by a sustained period of pronounced suppression.

These behavioral and neuronal results demonstrate a cortical selection mechanism that rapidly inverts a pop-out signal to pop-in for an entire feature dimension thereby facilitating goal-directed visual search in the presence of salient distractors.

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Neuroscience Tools Structure May Lead to Next Gen Versions – Newswise

February 26, 2023 medical

Newswise In order to more fully understand how diseases arise in the brain, scientists must unravel the intricate way neurons relay messages (either chemical or electrical) along a complex web of nerve cells. One way is by using a tool called DREADDs, which stands forDesignerReceptorsActivated byDesignerDrugs.

When introduced to a nerve cell or neuron, DREADDs acts like a specialized lock that only works when a key in the form of a synthetic designer drug fits into that lock. DREADDs can enable researchers to turn specific cell functions on or off to examine groups of neurons in circuits more precisely.(see Animations)

Now, a University of Maryland School of Medicine researcher and his colleagues at the University of North Carolina Chapel Hill (UNC) have unveiled the structure of these DREADDs that will pave the way for creating the next generation of these tools. This step ultimately will bring them closer to an elusive goal understanding the underpinnings of brain disorders, such as schizophrenia, substance abuse, epilepsy, and Alzheimers, in order to develop more effective drugs to treat them.

The research team published their findings in a recent issue ofNature.

These findings provide atomic clarity into the nature of DREADD receptors bound to their drugs, resulting from the culmination of all these technologies converging at the right place and right time,said study authorJonathan Fay, PhD,Assistant Professor of Biochemistry and Molecular Biology at UMSOM. This knowledge will allow this tool to be further refined and optimized. We were previously limited in how to upgrade their designs because we didnt fully understand how they worked at the structural level.

Hundreds of labs around the world now use the DREADD tool, which was developed at UNC. Scientists there designed these receptor proteins to react only to uniquely designed drugs that are pharmacologically inert because they only bind to the DREADD protein receptor.

For this new study, researchers used a newer imaging technology, known as cryogenic electron microscopy, to determine the molecular structure of DREADD receptors with the drugs. This process flash-freezes the DREADDs in a way that does not form traditional ice crystals, but instead creates a sort of slurry that allows some movement in the molecules. This technique allowed researchers to determine the DREADDs structure when other older molecular imaging methods failed. The researchers observed inhibitory (turning off cell functions) or stimulatory (turning on cell functions) DREADD receptors bound to each of two different designer drugs.

The researchers also compared the structure of the natural brain receptor from which DREADDs originated to see how it differed from DREADDs. The original brain receptor, found in the cell membrane of neurons, traditionally binds to a molecule involved in learning and memory. By changing two of the natural receptors building blocks, the engineered DREADD receptor binds better to its own laboratory-designed drugs rather than to the original memory moleculea process they visualized through their experiments.

With this imaging technique,we could see that the genetic changes in the DREADDs opened up the space where the memory molecule normally binds, allowing the new designer drugs to slip in. We could see that shape of the space changed as well, contributing to why the new drugs fit better, said Dr. Fay.

The class of receptors from which DREADDs originated are often the intended targets of many therapeutics. However, various drugs bind to several kinds of receptors or activate others in unintended ways. The result might be a beneficial effect, but also can result in side effects.

Because of the precise way in which these designer drugs in DREADDs bind so specifically, it is likely possible that researchers will one day eventually develop targeted therapies for many of these other similar receptors without the cross-reactivity and unpleasant side effects,said UMSOM DeanMark T. Gladwin, MD, Vice President for Medical Affairs, University of Maryland, Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor.

Although the microscopy-related part of this study occurred at UNC, UMSOM also has high-tech structural biology capabilities in theirCenter for Biomolecular Therapeutics (CBT), where researchers determine the structures of the human bodys proteins to better develop new drugs to treat a variety of diseases. Dr. Fay plans to use CBTs facilities to analyze the structure of other brain receptors, as well as to continue his collaboration with UNC on potential DREADD 2.0 versions.

A major focus of UMSOMs research, as evidenced by the launch of the University of Maryland-Medicine Institute for Neuroscience Discovery(UM-MIND)in late 2022 includes neuroscience and brain-related diseases. Dr. Fays work directly contributes towards these institutional priorities.

This research study was funded by a National Institutes of Health - National Institute of Diabetes and Digestive and Kidney Diseases grant (U24DK116194).

About the University of Maryland School of Medicine

Now in its third century, the University of Maryland School of Medicine was chartered in 1807 as the first public medical school in the United States.It continues today as one of the fastest growing, top-tier biomedical research enterprises in the world with 46 academic departments, centers, institutes, and programs, and a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of Medicineand the National Academy of Sciences, and a distinguished two-time winner of the Albert E. Lasker Award in Medical Research.With an operating budget of more than $1.3 billion, the School of Medicine works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic, and clinically based care for nearly 2 million patients each year. The School of Medicine has nearly $600 million in extramural funding, with most of its academic departments highly ranked among all medical schools in the nation in research funding.As one of the seven professional schools that make up the University of Maryland, Baltimore campus, the School of Medicine has a total population of nearly 9,000 faculty and staff, including 2,500 students, trainees, residents, and fellows. The combined School of Medicine and Medical System (University of Maryland Medicine) has an annual budget of over $6 billion and an economic impact of nearly $20 billion on the state and local community. The School of Medicine, which ranks as the8thhighestamong public medical schools in research productivity (according to the Association of American Medical Colleges profile) is an innovator in translational medicine, with 606 active patents and 52 start-up companies.In the latestU.S. News & World Reportranking of the Best Medical Schools, published in 2021, the UM School of Medicine isranked #9among the 92 public medical schoolsin the U.S., and in the top 15 percent(#27) of all 192public and privateU.S. medical schools.The School of Medicine works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visitmedschool.umaryland.edu

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Neuroscience

Psychedelics May Help People Reinvent Themselves – Neuroscience News

February 26, 2023 medical

Summary: In addition to helping treat mental health disorders, psychedelic treatments can help people overcome addictions. A new study reports psychedelics can help smokers quit nicotine and remain smoke-free for at least five years.

Source: University of Cincinnati

Researchers from the University of Cincinnati examined the post-treatment journals kept by participants in a 2014 smoking cessation study that found psychedelics were effective in helping some people quit smoking for years.

In a new paper published in theKennedy Institute of Ethics Journal, researchers analyzed the participants own words and found that psychedelics combined with talk therapy often helped longtime smokers see themselves as nonsmokers. This new core identity might help explain why 80% of participants were able to stopsmokingfor six months and 60% remained smoking-free after five years.

The 2014 study by researchers at Johns Hopkins University found that participants who wanted to quit smoking and used psilocybin, the active hallucinogenic ingredient inpsychedelicmushrooms, combined withcognitive behavioral therapywere far more likely to succeed than those who try other traditional quit-smoking methods.

Lead author and University of Cincinnati postdoctoral researcher Nee Devenot said the results demonstrate the potential psychedelics have to reshape self-perceptions to help people break free of old habits or addictions in the face of lifes daily triggers and temptations.

We saw again and again that people had this feeling that they were done with smoking and that they were a nonsmoker now, Devenot said.

She studies the science, history and culture of psychedelics in UCs Institute for Research in Sensing.

Devenot said this new sense of self might help arm people against temptation or old triggers.

If you want to give up meat but you smell a delicious steak, it might be hard to resist, she said. But if you identify as a vegetarian and your sense of who you are is someone who does not eat meat, that identity helps encourage a different choice.

During the smoking cessation study, therapists gave participants guided imagery exercises in which they were asked to envision smoking as a behavior external to their core identity. The participants documented their experience in writing.

One guided imagery exercise from the study framed nicotine addiction as an external force, manipulating behavior for its own ends like the zombie-creating fungus in HBOs popular series The Last of Us.

Like the Cordyceps fungi that functionally transforms insects into zombified marionettes to serve the fungis own reproductive purposes, smoking behavior is characterized as a form of parasitic manipulation, the study found.

Albert Garcia-Romeu, an assistant professor of psychiatry andbehavioral sciencesat Johns Hopkins University, said psilocybin could serve as a catalyst to help motivate and inspire people to make a change with the help of cognitive behavioral therapy.

Cognitive behavioral therapy asks us to tune into the thoughts and feelings that we experience in our day-to-day lives and how those relate to our behaviors, Garcia-Romeu said. In turn, people often tend to build a narrative or sense of self around those cognitions and behaviors.

This sets the stage for actually having the psilocybin experience, which can both provide novel insights and perspectives as well as serve as a marker of that identity shift like a rite of passage, signifying the change for instance from smoker to nonsmoker.

Devenot said the experiments sample size was relatively small at just 15 participants. But the results are encouraging.

I feel that I am somehow fundamentally different to yesterday, one participant wrote. I guess I feel like some sort of metamorphosis has taken place!

Some participants said the treatment with psilocybin made quitting feel easy compared to past experiences. Another said the cravings for nicotine used to be unbearable. But during the dosing session, the participant was unable even to imagine craving a cigarette.

The concept seems firmly cemented into my reality even today, that cravings are not something that are real, one said.

How do psychedelics help with this transformation?

Devenot says people often get stuck in the same ruts of behavior, responding the same way to stressors or other triggers. She likens it to a downhill skier who uses the same grooved path down the mountain that they have used a thousand other times.

Its not that simple, but its a metaphor for how we talk about psychedelics, Devenot said.

Psychedelics have been compared to skiing in fresh snow, she said. The entrenched grooves of bad habits might not have as much pull on our skis, so we can lay down other paths.

Were looking for ways to help people shift behaviors and overcome the inertia of their habits that are more in line with their goals and aspirations, Devenot said. Thats why psychedelics are of wider interest to researchers.

Author: Michael MillerSource: University of CincinnatiContact: Michael Miller University of CincinnatiImage: The image is in the public domain

Original Research: Closed access.Psychedelic Identity Shift: A Critical Approach to Set And Setting by Nee Devenot et al. Kennedy Institute of Ethics Journal

Abstract

Psychedelic Identity Shift: A Critical Approach to Set And Setting

While the literature on psychedelic medicine emphasizes the importance of set and setting alongside the quality of subjective drug effects for therapeutic efficacy, few scholars have explored the therapeutic frameworks that are used alongside psychedelics in the lab or in the clinic.

Based on a narrative analysis of the treatment manual and post-session experience reports from a pilot study of psilocybin-assisted treatment for tobacco smoking cessation, this article examines how therapeutic frameworks interact with the psychedelic substance in ways that can rapidly reshape participants identity and sense of self.

We identified multiple domains relating to identity shift that appear to serve as smoking cessation mechanisms during psilocybin sessions, each of which had an identifiable presence in the manualized treatment.

As psychedelic medicine becomes mainstream, consensual and evidence-based approaches to psychedelic-assisted identity shift that respect patient autonomy and encourage empowerment should become areas of focus in the emergent field of psychedelic bioethics.

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Neuroscience

Could ChatGPT Replace Doctors in Infection Consulting Scenarios? – Neuroscience News

February 26, 2023 medical

Summary: While there is clear potential to use ChatGPT in a clinical setting, researchers say the AI algorithm may not yet be a reliable way of replacing the family doctor, especially when it comes to making effective decisions about prescribing antibiotics for infections.

Source: University of Liverpool

Researchers from the University of Liverpool have tested whether the AI-powered chatbot ChatGPT could be used to make decisions about prescribing patients with antibiotics.

In a letter published inThe Lancet Infectious Diseases, academics from the Institute of Systems, Molecular and Integrative Biology show that, whileartificial intelligencecant yet replace thefamily doctor, there is clear potential for technology to play a role inclinical practice.

The researchers presented ChatGPT with eight hypothetical infection scenarios which people would commonly consult their doctor about (such as a chest infection). They then assessed the advice delivered by the technology for its appropriateness, consistency and its impact onpatient safety.

Theassessmentfound that ChatGPT understood the scenarios and provided coherent answers, including disclaimers, and signposting patients to sources of advice. It also appeared to understand the need to only prescribeantibioticswhen there was evidence of bacterial infection.

However, ChatGPT provided unsafe advice in complex scenarios and where important information was not explicitly provided.

Interestingly, the AI tended to focus on the type of antibiotic prescribed in each scenario rather than other factors, reflecting the assumptions often initially made by doctors during consultation.

Following the experiment, the researchers have now developed a checklist for standards that AI should meet in order to be considered for use in clinical practice in the future.

Co-author of the letter, Dr. Alex Howard said, It was fascinating to see the potential of artificial intelligence in health care demonstrated through this experiment testing ChatGPTs ability to give antibiotic treatment advice.

With the rise of antibiotic resistance posing a significant threat to global health, the ability of AI to provide accurate and safe treatment advice could revolutionize the way we approach patient care. We look forward to further exploration of this technology and its implications for the future of health care.

Author: Press OfficeSource: University of LiverpoolContact: Press Office University of LiverpoolImage: The image is in the public domain

Original Research: Open access.ChatGPT and antimicrobial advice: the end of the consulting infection doctor? by Alex Howard et al. Lancet Infectious Diseases

Abstract

ChatGPT and antimicrobial advice: the end of the consulting infection doctor?

Generative artificial intelligence (AI) models have proliferated in the past 2 years. ChatGPTa large language model (LLM) developed by OpenAI (San Francisco, CA)mimics natural language and solves cognitive problems by reinforcing learning from online resources using human feedback.

Despite access to limited medical data, ChatGPT has medical licensing examination performance as an undergraduate third-year medical student, and has, therefore, stimulated urgent discussions within medicine.

Stokel-Walker and van Noorden discuss the implications of generative AI for science and describe how ChatGPT could answer some open-ended medical queries almost as well as the average human physician could, although it still had shortcomings and unreliabilities.

Neuroscience

Study Finds Link Between Chronic Pain and Dementia – Neuroscience News

February 26, 2023 medical

Summary: People with chronic pain in multiple parts of the body have a higher risk of developing dementia and accelerated cognitive decline.

Source: Chinese Academy of Science

A research team led by Dr. TU Yiheng from the Institute of Psychology of the Chinese Academy of Sciences has found that people with chronic pain in multiple parts of the body had a higher risk of dementia and experienced broader and faster cognitive decline, including memory, executive function, learning, and attention.

The study was published online inPNASon Feb. 20.

Multisite chronic pain, where pain is experienced in multiple anatomical locations, affects almost half of chronic pain patients and has been found to place a greater burden on patients overall health. However, it has not been clear whether people with multisite chronic pain suffered from aggravated neurocognitive abnormalities.

In this study, after analyzing the records of 354,943 people in the UK Biobank cohort, the researchers found that the risk of neurocognitive abnormality increased with each additional pain site and was mediated by atrophy in the hippocampus, the part of the brain responsible for memory.

Since hippocampal volume decreases with age, the researchers equated the magnitude of the effect of hippocampal atrophy in patients with multisite chronic pain to the effect of aging in healthy people with an average age of 60.

Multisite chronic pain may lead to up to eight years of accelerated hippocampal aging, an effect that may underlie a series of cognitive burdens, said Dr. TU, corresponding author of the study.

The study provides a quantitative understanding of the impact of chronic pain on cognitive function and the risk of dementia, laying an important foundation for future research into the relationship between chronic pain and cognitive impairment.

It also highlights the excessive burden of multisite chronic pain on patients cognition and the brain, and the need to address the overlapping nature of pain conditions in both basic research and clinical studies.

Funding: This study was supported by the STI2030-Major Projects Program, the National Natural Science Foundation of China, and the Scientific Foundation of the Institute of Psychology of CAS, among other sources.

Author: TU YihengSource: Chinese Academy of ScienceContact: TU Yiheng Chinese Academy of ScienceImage: The image is in the public domain

Original Research: Closed access.Elevated dementia risk, cognitive decline, and hippocampal atrophy in multisite chronic pain by TU Yiheng et al. PNAS

Abstract

Elevated dementia risk, cognitive decline, and hippocampal atrophy in multisite chronic pain

Numerous studies have investigated the impacts of common types of chronic pain (CP) on patients cognitive function and observed that CP was associated with later dementia. More recently, there is a growing recognition that CP conditions frequently coexist at multiple body sites and may bring more burdens on patients overall health.

However, whether and how multisite CP (MCP) contributes to an increased risk of dementia, compared to single-site CP (SCP) and pain-free (PF), is largely unclear.

In the current study, utilizing the UK Biobank cohort, we first investigated dementia risk in individuals (n = 354,943) with different numbers of coexisting CP sites using Cox proportional hazards regression models. We then applied generalized additive models to investigate whether MCP leads to excessive deterioration of participants (n = 19,116) cognition and brain structure.

We found that individuals with MCP were associated with significantly higher dementia risk, broader and faster cognitive impairment, and greater hippocampal atrophy than both PF individuals and those with SCP.

Moreover, the detrimental effects of MCP on dementia risk and hippocampal volume aggravated along with the number of coexisting CP sites. Mediation analyses further revealed that the decline of fluid intelligence in MCP individuals was partially mediated by hippocampal atrophy.

Our results suggested that cognitive decline and hippocampal atrophy interact biologically and may underlie the increased risk of dementia associated with MCP.

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Medtronic’s Q3 Exceeds Expectations On Strong Cardiovascular … – Yahoo Finance

February 26, 2023 medical

Medtronic Plc's(NYSE: MDT)Q3 FY23 sales of $7.73 billionflat Y/Y on a reported basis and increased 4.1% organically, beating the consensus of $7.53 billion.

The organic comparison excludes a $379 million negative impact from foreign currency translation and a $26 million contribution from its fiscal first quarter acquisition of Intersect ENT, which is reported in the Specialty Therapies division in the Neuroscience Portfolio.

The adjusted EPS of $1.30 exceeded the consensus of $1.27, and decreased by 4%.

Organic revenue results reflect strong performances in the Cardiovascular and Neuroscience portfolios, Diabetes markets outside the U.S., and improved product availability across certain businesses, partially offset by unfavorable impacts from ventilator sales.

Medtronic's heart device unit sales increased 1% Y/Y (+7% organic) to $2.77 billion.

Spine & neurosurgery product segment sales increased 5% Y/Y (+7%) to $2.25 billion.

Diabetes revenue of $570 million decreased by 2% (+3%).

The Medical Surgical Portfolio sales decreased 7% (-2% organic) to $2.14 billion.

Guidance:The company expects Q4 FY23 organic revenue growth of 4.5% to 5.0%. Currency headwinds could affect Q4 sales by approximately $165-$215 million.

Medtronic tightens FY23 EPS outlook to $5.28 - $5.30 ($5.25 - $5.30 Prior), compared to the consensus of $5.44.

Price Action:MDT shares are up 2.49% at $86.91 during the premarket session on the last check Tuesday.

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This article Medtronic's Q3 Exceeds Expectations On Strong Cardiovascular And Neuroscience Performance, Tightens FY23 Outlook originally appeared on Benzinga.com

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Neuroscience

Any Regular Physical Activity at Any Age Linked to Better Brain … – Neuroscience News

February 26, 2023 medical

Summary: At any age, regular exercise or physical activity helps to maintain brain function during old age. However, maintaining a frequent workout schedule throughout life was linked to better mental acuity, memory, and cognition later in life.

Source: BMJ

Any regular leisure time physical activity at any age is linked to better brain function in later life, but maintaining an exercise routine throughout adulthood seems to be best for preserving mental acuity and memory, suggests a long term study published online in theJournal of Neurology Neurosurgery & Psychiatry.

Even though factoring in childhood cognitive ability, household income, and education weakened the observed associations, the findings remained statistically significant.

Physical activity is modestly associated with a lower risks of dementia, cognitive decline, and loss of later life mental acuity. But its not known whether the timing, frequency, or maintenance of leisure time physical activity across the life course might be key to later life cognitive abilities.

The researchers were particularly keen to know if physical activity might be most beneficial in specific sensitive periods across the life course, or across multiple time periods.

To try and find out, they looked at the strength of associations between a range of cognitive tests at age 69 and reported leisure time physical activity at the ages of 36, 43, 53, 60-64, and 69 in 1417 people (53% women) taking part in the 1946 British birth cohort study.

Physical activity levels were categorised as: inactive; moderately active (14 times/month); most active (5 or more times/month), and summed across all 5 assessments to create a total score ranging from 0 (inactive at all ages) to 5 (active at all ages).

Some 11% of participants were physically inactive at all 5 time points; 17% were active at one; 20% were active at two and three; 17% were active at four and 15% at all five.

Cognitive performance at age 69 was assessed using the validated ACE-111, which tests attention and orientation, verbal fluency, memory, language, and visuospatial function, plus by tests of verbal memory (word learning test) and processing speed (visual search speed).

Factors associated with a heightened risk of cognitive declinecardiovascular and mental health, and carriage of the APOE-4 genewere also assessed to see if these modified any observed associations.

Analysis of the results showed that being physically active at all 5 time points was associated with higher cognitive performance, verbal memory, and processing speed at the age of 69.

The effect sizes were similar across all adult ages, and for those who were moderately and most physically active, suggesting that being physically active at any time in adulthood, even if participating as little as once per month, is linked with higher cognition, write the researchers.

But the strongest association was observed for sustained cumulative physical activity and later life cognition, and for those who were most physically active at all ages.

The positive association between cumulative physical activity and later life cognitive performance was partly explained by childhood cognition, socioeconomic position, and education.

But the effect remained significant when these were factored in, and the associations werent explained by differences in later life cardiovascular or mental health.

Together, these results suggest that the initiation and maintenance of physical activity across adulthood may be more important than the timing.or the frequency of physical activity at a specific period, say the researchers.

This is an observational study, and as such, cant establish cause, and the researchers acknowledge various limitations to their findings.

The study included only White participants and had a disproportionately high attrition rate among those who were socially disadvantaged. No information was available on exercise intensity, duration, or adherence either.

But they nevertheless conclude: Our findings support guidelines to recommend participation in any physical activity across adulthood and provide evidence that encouraging inactive adults to be more active at any time, and encouraging already active adults to maintain activity, could confer benefits on later life cognition.

Author: Press OfficeSource: BMJContact: Press Office BMJImage: The image is in the public domain

Original Research: Open access.Timing of physical activity across adulthood on later life cognition: 30 years follow-up in the 1946 British birth cohort by Sarah-Naomi Jameset al. Journal of Neurology Neurosurgery & Psychiatry

Abstract

Timing of physical activity across adulthood on later life cognition: 30 years follow-up in the 1946 British birth cohort

Background

To assess how timing, frequency and maintenance of being physically active, spanning over 30 years in adulthood, is associated with later-life cognitive function.

Methods

Participants (n=1417, 53% female) were from the prospective longitudinal cohort study, 1946 British birth cohort. Participation in leisure time physical activity was reported five times between ages 36 and 69, categorised into: not active (no participation in physical activity/month); moderately active (participated 14 times/month); most active (participated 5 or more times/month). Cognition at age 69 was assessed by tests of cognitive state (Addenbrookes Cognitive Examination-III), verbal memory (word learning test) and processing speed (visual search speed).

Results

Being physically active, at all assessments in adulthood, was associated with higher cognition at age 69. For cognitive state and verbal memory, the effect sizes were similar across all adult ages, and between those who were moderately and most physically active. The strongest association was between sustained cumulative physical activity and later-life cognitive state, in a dose-response manner. Adjusting for childhood cognition, childhood socioeconomic position and education largely attenuated these associations but results mainly remained significant at the 5% level.

Conclusions

Being physically active at any time in adulthood, and to any extent, is linked with higher later-life cognitive state, but lifelong maintenance of physical activity was most optimal. These relationships were partly explained by childhood cognition and education, but independent of cardiovascular and mental health and APOE-E4, suggestive of the importance of education on the lifelong impacts of physical activity.

Neuroscience

Temperature Changes in the Brain Found to Affect Neuronal Activity – Neuroscience News

February 26, 2023 medical

Summary: Small temperature increases while stimulating the brain can alter brain activity, sometimes with negative consequences.

Source: Yale

Last summer, devastating wildfires raged across frozen regions in Siberia, Alaska, and Canada. They were caused in part by rising global temperatures, which accelerated the ability of bacteria in the soil to metabolize plant and animal matter.

These environmental phenomena demonstrated a basic principle of physicstemperature is one of the main components of a chemical reaction and even seemingly small changes can result in catastrophic impacts. Heat a Siberian peat bog faster than it can release carbon into the atmosphere, and you get a wildfire on your handseven in subzero temperatures.

Researchers now know that the physics behind this environmental phenomenon apply also to brain activity. In a paper published in theJournal of Neural Engineering, researchers found that small increases in temperature while stimulating the brain can profoundly alter brain activity, sometimes with negative consequences.

Steven Schiff, MD, vice chair for global health in Neurosurgery at Yale School of Medicine, specializes in the intersection between engineering and neurosurgery, which gives him the background to apply principles of physics to the biological processes of the brain.

Since activity in wires produce heat, all electric and magnetic stimulation of the brain deposits thermal energy in the brain. Schiff and his co-authors theorized that electric stimulating brain devices such as Deep Brain Stimulation, used in epilepsy and Parkinsons disease patients, must lead to temperature changes in the brain.

Temperature changes in the brain also affect the firing of neurons. Lining the membranes of nerve cells are molecular pumps that electrically charge up the cells with energy that they release during brain activity. The researchers were able to prove that if cells are heated faster than the charges can adjust, then they may either produce more neuronal activity or less than usual.

Even small changes in temperature due to electrical stimulation of the brain less than 1C, could lead to substantial changes in neuronal activity. As neurons warm they can go silent. Let them cool back to their normal temperature and they can get very excitable.

Seeing these dramatic effects onbrain activityfrom small changes in temperature means that we now need to take such small temperature changes into account, says Schiff, lead author of the study.

[Physicist James] Joule, long ago, taught us that there is no way around this problem. If you pass electrical current through small conductive wires to generate electrical or magnetic fields to stimulate the brain, you generate heat both in the wires and in the conductive brain.

This paradigm shifting paper was presented in December 2022, at the American Epilepsy Society meeting in Washington DC where it was received with great interest.

How these temperature changes affect the patient and how they could be harnessed to improve outcomes remains to be seen. Inclinical settings, surgeons have observed previously that a common side effect to implanting nervous system stimulators is that the activity of stimulated brain often decreases with either electrical or magnetic stimulation.

The paper points to a strong plausible cause for this phenomenon. If true, Dr. Schiff says, this finding could help doctors more accurately calibrate the use of these devices.

This paper is a true tour de force of combining different models of physical behavior to re-examine some old standards,' says William Stacey, MD, Ph.D., associate professor of the department of neurology and biomedical engineering at the University of Michigan.

The combination of modeling with clever experimentation provided the very intriguing and unexpected result that heat might suppress neural firing. Perhaps this model might also provide some novel methods to manipulate neural activity.

Daniel M. Goldenholz, MD, Ph.D., assistant professor of epilepsy at Harvard, and author of a recent paper on why focal cooling is important for the future of treating focal epilepsy, found the results important as well.

I think the work from Dr. Schiff and colleagues highlights the great importance oftemperaturechanges inbraintissue and will likely be relevant in treatments of epilepsy that may include focal cooling. These fluctuations need to be better understood and accounted for if we want our therapies to become more accurate.

I would be very excited to see how Dr. Schiffs results are harnessed in the future for treatment of seizures and for neuromodulation, says Goldenholz.

Author: Jennifer ChenSource: YaleContact: Jennifer Chen YaleImage: The image is in the public domain

Original Research: Open access.Thermal effects on neurons during stimulation of the brain by TaeKen Kim et al. Journal of Neural Engineering

Abstract

Thermal effects on neurons during stimulation of the brain

All electric and magnetic stimulation of the brain deposits thermal energy in the brain. This occurs through either Joule heating of the conductors carrying current through electrodes and magnetic coils, or through dissipation of energy in the conductive brain.

Objective.

Although electrical interaction with brain tissue is inseparable from thermal effects when electrodes are used, magnetic induction enables us to separate Joule heating from induction effects by contrasting AC and DC driving of magnetic coils using the same energy deposition within the conductors. Since mammalian cortical neurons have no known sensitivity to static magnetic fields, and if there is no evidence of effect on spike timing to oscillating magnetic fields, we can presume that the induced electrical currents within the brain are below the molecular shot noise where any interaction with tissue is purely thermal.

Approach.

In this study, we examined a range of frequencies produced from micromagnetic coils operating below the molecular shot noise threshold for electrical interaction with single neurons.

Main results.

We found that small temperature increases and decreases of 1C caused consistent transient suppression and excitation of neurons during temperature change. Numerical modeling of the biophysics demonstrated that the Na-K pump, and to a lesser extent the Nernst potential, could account for these transient effects. Such effects are dependent upon compartmental ion fluxes and the rate of temperature change.

Significance.

A new bifurcation is described in the model dynamics that accounts for the transient suppression and excitation; in addition, we note the remarkable similarity of this bifurcations rate dependency with other thermal rate-dependent tipping points in planetary warming dynamics.

These experimental and theoretical findings demonstrate that stimulation of the brain must take into account small thermal effects that are ubiquitously present in electrical and magnetic stimulation.

More sophisticated models of electrical current interaction with neurons combined with thermal effects will lead to more accurate modulation of neuronal activity.

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Temperature Changes in the Brain Found to Affect Neuronal Activity - Neuroscience News

Neuroscience

Domestic Abuse in Pregnancy Linked to Structural Brain Changes in … – Neuroscience News

February 26, 2023 medical

Summary: Babies born to mothers who experience domestic violence during pregnancy have altered brain development and changes in brain structure. In females, maternal exposure to IPV was associated with a smaller amygdala, a brain area associated with social and emotional development. In males, the caudate nucleus size was increased. This brain area is associated with multiple functions including memory, learning, reward, and movement. The findings may explain why children of mothers who experience domestic abuse are more likely to suffer from mental health problems later in life.

Source: University of Bath

Domestic abuse against women during pregnancy can potentially have a significant impact on how the unborn babys brain develops, according to a new study.

Researchers at the University of Bath, working in collaboration with researchers from the University of Cape Town, analyzedbrain scansof 143 South African infants whose mothers had been subject tointimate partner violence(IPV) during pregnancy. Intimate partner violence includes emotional, physical and/or sexual abuse or assault.

Brain MRI scans were taken when infants were just 3 weeks old on average so any changes that were observed are likely to have developed inside the womb.

Publishing their findings in the journalDevelopmental Cognitive Neuroscience, the research team report thatmaternal exposureto IPV during pregnancy is associated with alterations inbrain structurein young infants identified shortly after birth.

This was evident even when the researchers took into account maternal alcohol use and smoking throughout pregnancy as well as pregnancy complications.

Importantly, the effects of IPV exposure may differ by the babys sex.

For girls, their mothers exposure to IPV during pregnancy was linked to a smaller amygdala, an area of thebraininvolved in emotional andsocial development.

For boys, IPV exposure was instead associated with a larger caudate nucleus, an area of the brain involved in multiple functions including the execution of movement, learning, memory, reward, and motivation.

Early changes to brain structures may explain why children whose mothers experience high levels of stress during pregnancy are more likely to have psychological issues in childhood or later life.

Sex differences in brain development may also help explain why girls and boys often develop different mental health problems. However, the researchers cautioned that the study did not analyze emotional andcognitive developmentin children.

Lead researcher, Dr. Lucy Hiscox from the Department of Psychology at Bath, explained, Our findings are a call to act on the three Rs of domestic violence awareness: recognize, respond, and refer. Preventing or quickly acting to help women escape domestic violence may be an effective way of supporting healthy brain development in children.

While previous studies have looked at the impact of maternal stress in pregnancy and its impacts on childrensbrain development, this is the first to examinedomestic abuse. The children involved in this study are now aged 8-9 years and follow-up research is testing whether the differences in brain structure seen at 3 weeks old persist, or are altered, as they age.

For this study, the team from Bath worked with researchers at the University of Cape Town (UCT) to analyze data from a major South African cohort study, the Drakenstein Child Health Study (DCHS), led by South African pediatrician Professor Heather Zar. The DCHS has been tracking 1,143 children since birth with data collection ongoing.

Co-author, Professor Kirsty Donald, a pediatric neurologist and Head of the Division of Developmental Pediatrics at UCT added, Strategies that help identify and support pregnant mums for multiple potential risks to their unborn babies will require an integrated health system approach and should be considered a public health priority.

Author: Andy DunneSource: University of BathContact: Andy Dunne University of BathImage: The image is in the public domain

Original Research: Open access.Antenatal maternal intimate partner violence exposure is associated with sex-specific alterations in brain structure among young infants: Evidence from a South African birth cohort by Lucy V. Hiscox et al. Developmental Cognitive Neuroscience

Abstract

Antenatal maternal intimate partner violence exposure is associated with sex-specific alterations in brain structure among young infants: Evidence from a South African birth cohort

Maternal psychological distress during pregnancy has been linked to adverse outcomes in children with evidence of sex-specific effects on brain development.

Here, we investigated whetherin uteroexposure to intimate partner violence (IPV), a particularly severe maternal stressor, is associated with brain structure in young infants from a South African birth cohort.

Exposure to IPV during pregnancy was measured in 143 mothers at 2832 weeks gestation and infants underwent structural and diffusion magnetic resonance imaging (mean age 3 weeks).

Subcortical volumetric estimates were compared between IPV-exposed (n=63; 52% female) and unexposed infants (n=80; 48% female), with white matter microstructure also examined in a subsample (IPV-exposed,n=28, 54% female; unexposed infants,n=42, 40% female).

In confound adjusted analyses, maternal IPV exposure was associated with sexually dimorphic effects in brain volumes: IPV exposure predicted a larger caudate nucleus among males but not females, and smaller amygdala among females but not males. Diffusivity alterations within white matter tracts of interest were evident in males, but not females exposed to IPV.

Results were robust to the removal of mother-infant pairs with pregnancy complications.

Further research is required to understand how these early alterations are linked to the sex-bias in neuropsychiatric outcomes later observed in IPV-exposed children.

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Domestic Abuse in Pregnancy Linked to Structural Brain Changes in ... - Neuroscience News