Tag: 14/2/23

Categories : Mental Health NeurologyTags : Leave a comment

Why do People Remember Emotional Events Better?

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Photo by Drew Coffman on Unsplash

Most people remember emotional events, like their wedding day, very clearly, but researchers are not sure how the human brain prioritises emotional events in memory. In a study published in Nature Human Behaviour, Joshua Jacobs, associate professor of biomedical engineering at Columbia Engineering, and his team identified a specific neural mechanism in the human brain that tags information with emotional associations for enhanced memory.

The team demonstrated that high-frequency brain waves in the amygdala, a hub for emotional processes, and the hippocampus, a hub for memory processes, are critical to enhancing memory for emotional stimuli. Disruptions to this neural mechanism, brought on either by electrical brain stimulation or depression, impair memory specifically for emotional stimuli.

Rising prevalence of memory disorders

The rising prevalence of memory disorders such as dementia has highlighted the damaging effects that memory loss has on individuals and society. Disorders such as depression, anxiety, and post-traumatic stress disorder (PTSD) can also feature imbalanced memory processes, especially with the COVID pandemic. Understanding how the brain naturally regulates what information gets prioritised for storage and what fades away could provide critical insight for developing new therapeutic approaches to strengthening memory for those at risk of memory loss, or for normalising memory processes in those at risk of dysregulation.

“It’s easier to remember emotional events, like the birth of your child, than other events from around the same time,” says Salman E. Qasim, lead author of the study, who started this project during his PhD in Jacobs’ lab at Columbia Engineering. “The brain clearly has a natural mechanism for strengthening certain memories, and we wanted to identify it.”

The difficulty of studying neural mechanisms in humans

Most investigations into neural mechanisms take place in animals such as rats, because such studies require direct access to the brain to record brain activity and perform experiments that demonstrate causality, such as careful disruption of neural circuits. But it is difficult to observe or characterise a complex cognitive phenomenon like emotional memory enhancement in animal studies.

To study this process directly in humans. Qasim and Jacobs analysed data from memory experiments conducted with epilepsy patients undergoing direct, intracranial brain recording for seizure localisation and treatment. During these recordings, epilepsy patients memorised lists of words while the electrodes placed in their hippocampus and amygdala recorded the brain’s electrical activity.

Studying brain-wave patterns of emotional words

Qasim found that participants remembered more emotionally rated words, such as “dog” or “knife,” better than more neutral words, such as “chair.” Whenever participants successfully remembered emotional words, high-frequency neural activity (30-128 Hz) would become more prevalent in the amygdala-hippocampal circuit, a pattern which was absent when participants remembered more neutral words, or failed to remember a word altogether. Analysing 147 participant, they found a clear link between participants’ enhanced memory for emotional words and the prevalence in their brains of high-frequency brain waves across the amygdala-hippocampal circuit.

“Finding this pattern of brain activity linking emotions and memory was very exciting to us, because prior research has shown how important high-frequency activity in the hippocampus is to non-emotional memory,” said Jacobs. “It immediately cued us to think about the more general, causal implications – if we elicit high-frequency activity in this circuit, using therapeutic interventions, will we be able to strengthen memories at will?”

Electrical stimulation disrupts memory for emotional words

In order to establish whether this high-frequency activity actually reflected a causal mechanism, Jacobs and his team formulated a unique approach to replicate the kind of experimental disruptions typically reserved for animal research. First, they analysed a subset of these patients who had performed the memory task while direct electrical stimulation was applied to the hippocampus for half of the words that participants had to memorise. They found that electrical stimulation, which has a mixed history of either benefiting or diminishing memory depending on its usage, clearly and consistently impaired memory specifically for emotional words.

Uma Mohan, another PhD student in Jacobs’ lab at the time and co-author on the paper, noted that this stimulation also diminished high-frequency activity in the hippocampus. This provided causal evidence that, by knocking out the brain activity pattern correlating with emotional memory, stimulation was also selectively diminishing emotional memory.

Depression acts similarly to brain stimulation

Qasim further hypothesized that depression, which can involve dysregulated emotional memory, might act similarly to brain stimulation. He analyzed patients’ emotional memory in parallel with mood assessments the patients took to characterize their psychiatric state. And, in fact, in the subset of patients with depression, the team observed a concurrent decrease in emotion-mediated memory and high-frequency activity in the hippocampus and amygdala.

“By combining stimulation, recording, and psychometric assessment, they were able to demonstrate causality to a degree that you don’t always see in studies with human brain recordings,” said Bradley Lega, a neurosurgeon and scientist at the University of Texas Southwestern Medical Center and not an author on the paper. “We know high-frequency activity is associated with neuronal firing, so these findings open new avenues of research in humans and animals about how certain stimuli engage neurons in memory circuits.”

Next steps

Qasim is now investigating how individual neurons in the human brain fire during emotional memory processes. Qasim and Jacobs hope that their work might also inspire animal research exploring how this high-frequency activity is linked to norepinephrine, a neurotransmitter linked to attentional processes that they theorise might be behind the enhanced memory for emotional stimuli. They also hope that future research will target high-frequency activity in the amygdala-hippocampal circuit to protect memory.

“Our emotional memories are one of the most critical aspects of the human experience, informing everything from our decisions to our entire personality,” Qasim added. “Any steps we can take to mitigate their loss in memory disorders or prevent their hijacking in psychiatric disorders is hugely exciting.”

Source: Columbia University School of Engineering and Applied Science.

Categories : Ageing Injury & TraumaTags : Leave a comment

Mandatory Cognitive Screening for Older Drivers Reduces Car Crashes

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Photo by Charlie Deets on Unsplash

New research published in the Journal of the American Geriatrics Society reports that motor vehicle collisions decreased after Japan implemented a mandatory cognitive screening test for older drivers when they renewed their drivers’ licences. For older pedestrians and cyclists, however, their number of collisions and injuries increased.

For the study, investigators analysed police-reported data on the number of collisions for drivers and injuries for pedestrians and cyclists among people aged 70 years or older in Japan from July 2012 to December 2019. As of March 2017, drivers aged 75 years or older who screen positive are required to see a physician before license renewal. If diagnosed with dementia, their licenses may be suspended or revoked.

From 2012 to 2019, there were 602 885 collisions for drivers and 196 889 injuries for pedestrians and cyclists among people aged 70 years or older. After the 2017 policy, collisions decreased among male drivers, and injuries increased among some age subgroups in both sexes. Cumulative estimated changes in the numbers of collisions and injuries from March 2017 to December 2019 were -3670 and 959, respectively.

“Safety measures need to be strengthened for older cyclists and pedestrians. We should also provide older people with necessary care to prepare for driving cessation and safe, alternative transport means,” said corresponding author Haruhiko Inada, PhD, a post-doctoral fellow at the Johns Hopkins Bloomberg School of Public Health.

Source: Wiley

Categories : Diseases, Syndromes and Conditions Immune SystemTags : Leave a comment

Training Cells to Fight Both Chronic Inflammatory and Infectious Diseases

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T cell
Scanning Electron Micrograph image of a human T cell. Credit: NIH/NIAID

Researchers from the University of Queensland have identified a pathway in cells that could be used to reprogram the body’s immune system to fight back against both chronic inflammatory and infectious diseases such as E. Coli.

Reporting their findings in the open-access journal PNAS, Dr Kaustav Das Gupta and Professor Matt Sweet found that a glucose-derived molecule in immune cells can both stop bacteria growing and dampen inflammatory responses.

According to Dr Das Gupta, the discovery is a critical step towards future therapeutics that train immune cells.

“The effects of this molecule called ribulose-5-phosphate on bacteria are striking – it can cooperate with other immune factors to stop disease-causing strains of the E. coli bacteria from growing,” Dr Das Gupta said.

“It also reprograms the immune system to switch off destructive inflammation, which contributes to both life-threatening infectious diseases such as sepsis as well as chronic inflammatory diseases like respiratory diseases, chronic liver disease, inflammatory bowel disease, rheumatoid arthritis, heart disease, stroke, diabetes and dementia.”

The research was carried out on a strain of E. coli bacteria, responsible for 80% of urinary tract infections and also a common cause of sepsis. Pre-clinical trials confirmed the role of this pathway in controlling bacterial infections.

Professor Sweet said that human cells were also used to demonstrate that ribulose-5-phosphate reduces the production of molecules that drive chronic inflammatory diseases.

“Host-directed therapies which train our immune systems to fight infections, will become increasingly important as more types of bacteria become resistant to known antibiotics,” Professor Sweet said.

“A bonus is that this strategy also switches off destructive inflammation, which gives it the potential to combat chronic disease.

“By boosting the immune pathway that generates ribulose-5-phosphate, we may be able to give the body the power to fight back against inflammatory and infectious diseases – not one, but two of the major global challenges for human health.”

Many current anti-inflammatory therapies target proteins on the outside of cells but because this pathway occurs inside cells, the researchers devised a new approach to target the pathway using mRNA technology.

Source: University of Queensland

Categories : Diet and Nutrition Neurodegenerative DiseasesTags : Leave a comment

Fructose Could Drive Alzheimer’s Disease

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An ancient human instinct for foraging, fuelled by fructose production in the brain, may hold clues to the development and possible treatment of Alzheimer’s disease (AD), according to a new study published recently in The American Journal of Clinical Nutrition.

The findings provide a new way of looking at the neurodegenerative disease.

“We make the case that Alzheimer’s disease is driven by diet,” said the study’s lead author Richard Johnson, MD, professor at the University of Colorado School of Medicine specializing in renal disease and hypertension. The study co-authors include Maria Nagel, MD, research professor of neurology at the CU School of Medicine.

Johnson and his team suggest that AD is a harmful adaptation of an evolutionary survival pathway used in animals and our distant ancestors during times of scarcity.

“A basic tenet of life is to assure enough food, water and oxygen for survival,” the study said. “Much attention has focused on the acute survival responses to hypoxia and starvation. However, nature has developed a clever way to protect animals before the crisis actually occurs.”

When threatened with the possibility of starvation, early humans developed a survival response which sent them foraging for food. Yet foraging is only effective if metabolism is inhibited in various parts of the brain. Foraging requires focus, rapid assessment, impulsivity, exploratory behavior and risk taking. It is enhanced by blocking whatever gets in the way, like recent memories and attention to time. Fructose, a kind of sugar, helps damp down these centers, allowing more focus on food gathering.

In fact, the researchers found the entire foraging response was set in motion by the metabolism of fructose whether it was eaten or produced in the body. Metabolizing fructose and its byproduct, intracellular uric acid, was critical to the survival of both humans and animals.

The researchers noted that fructose reduces blood flow to the brain’s cerebral cortex involved in self-control, as well as the hippocampus and thalamus. Meanwhile, blood flow increased around the visual cortex associated with food reward. All of this stimulated the foraging response.

“We believe that initially the fructose-dependent reduction in cerebral metabolism in these regions was reversible and meant to be beneficial,” Johnson said. “But chronic and persistent reduction in cerebral metabolism driven by recurrent fructose metabolism leads to progressive brain atrophy and neuron loss with all of the features of AD.”

Johnson suspects the survival response, what he calls the `survival switch,’ that helped ancient humans get through periods of scarcity, is now stuck in the `on’ position in a time of relative abundance. This leads to the overeating of high fat, sugary and salty food prompting excess fructose production.

Fructose produced in the brain can lead to inflammation and ultimately Alzheimer’s disease, the researchers theorised. Animals given fructose show memory lapses, a loss in the ability to navigate a maze and inflammation of the neurons.

“A study found that if you keep laboratory rats on fructose long enough they get tau and amyloid beta proteins in the brain, the same proteins seen in Alzheimer’s disease,” Johnson said. “You can find high fructose levels in the brains of people with Alzheimer’s as well.”

Johnson suspects that the tendency of some AD patients to wander off might be a vestige of the ancient foraging response.

The study said more research is needed on the role of fructose and uric acid metabolism in AD.

“We suggest that both dietary and pharmacologic trials to reduce fructose exposure or block fructose metabolism should be performed to determine if there is potential benefit in the prevention, management or treatment of this disease,” Johnson said.

Source: University of Colorado Anschutz Medical Campus

Categories : NeurologyTags : Leave a comment

‘Love Hormone’ Oxytocin’s Role may be Overblown

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Disagreeing couple
Photo by Monstera from Pexels

The vital role of the ‘love hormone’ oxytocin for social attachments is being called into question. More than 40 years of pharmacological and behavioural research has pointed to oxytocin receptor signalling as an essential pathway for the development of social behaviours in prairie voles, humans, and other species, but a genetic study published in the journal Neuron shows that voles can form enduring attachments with mates and provide parental care without oxytocin receptor signalling.

Prairie voles are one of only a few monogamous mammalian species. After mating, they form lifelong partnerships known as “pair-bonds.” Pair-bonded voles share parental responsibilities, prefer the company of their partner over unknown members of the opposite sex, and actively reject potential new partners. Previous studies that used drugs to block oxytocin from binding to its receptor found that voles were unable to pair-bond when oxytocin signalling was blocked.

Neuroscientists Devanand Manoli of UCSF and Nirao Shah of Stanford University wanted to know whether pair-bonding was really controlled by oxytocin receptor signalling. To test this, they used CRISPR to generate prairie voles that lack functional oxytocin receptors. Then, they tested these mutant oxytocin-receptor-less voles to see whether they could form enduring partnerships with other voles. To their surprise, the mutant voles formed pair-bonds just as readily as normal voles.

“We were all shocked that no matter how many different ways we tried to test this, the voles demonstrated a very robust social attachment with their sexual partner, as strong as their normal counterparts,” says Manoli.

Next, the researchers wondered whether oxytocin receptor signaling is similarly dispensable for its other functions – parturition, parenting (which, in prairie voles, is a shared responsibility between the two parents), and milk release during lactation.

“We found that mutant voles are not only able to give birth, but actually nurse,” says Shah. Both male and female mutants engaged in the usual parental behaviours of huddling, licking, and grooming, and were able to rear pups to weaning age.

However, the mutant prairie voles did have limited milk release compared to normal voles. As a result, fewer of their pups survived to weaning age, and those that did survive were smaller compared to the pups of normal prairie voles. The fact that the voles could nurse at all is in contrast to equivalent studies in oxytocin receptor-deficient mice, who completely failed to lactate or nurse, and whose pups consequently died within a day or so of being born. The authors hypothesize that this species difference could be due to the inbred nature of laboratory mouse strains in contrast to the genetically heterogenous voles. “It could be that inbreeding in mice has selected for a large dependence on oxytocin signalling, or this may represent a species-specific role of oxytocin receptor signalling,” says Shah.

When asked why their results differ from previously published studies that used drugs to block oxytocin receptor signalling, the authors point to the key difference between genetic and pharmacological studies: precision. “Drugs can be dirty,” says Manoli, “in the sense that they can bind to multiple receptors, and you don’t know which binding action is causing the effect. From a genetics perspective, we now know that the precision of deleting this one receptor, and subsequently eliminating its signalling pathways, does not interfere with these behaviours.”

“For at least the last ten years people have been hoping for the possibility of oxytocin as a powerful therapeutic for helping people with social cognitive impairments due to conditions ranging from autism to schizophrenia,” Manoli says. “This research shows that there likely isn’t a magic bullet for something as complex and nuanced as social behaviour.”

Another key difference is that, whereas most pharmacological studies suppress oxytocin receptor signalling in adult animals, this study switched it off when the voles were embryos. “We’ve made a mutation that starts from before birth,” says Shah. “It could be that there are compensatory or redundant pathways that kick-in in these mutant animals and mask the deficits in attachment, parental behaviours, and milk let-down.”

Working with prairie voles presented an obstacle, but one worth overcoming. Because prairie voles are not commonly used in genetic studies like laboratory mice, the team needed to develop all of their molecular tools and protocols from scratch. Now that they have these vole-specific pipelines and tools, the authors are excited about the doorways this opens, both for them and for other researchers.

“We’re very happy to be part of a community and to have this technology that we can share,” says Manoli. “Now we have this trove that we can start to mine. There are so many other questions that prairie voles could be interesting and useful for answering, both in terms of potential clinical implications for models of anxiety or attachment and also for basic comparative biology.”

Source: News-Medical.Net