Tag: 13/1/23

Categories : NeurologyTags :

MRI Scans Reveal How Horror Movies Terrify Us

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Photo by Daniel Jensen on Unsplash

Finnish researchers at the University of Turku mapped the brain activity of (un)lucky participants who watched two of the highest rated horror movies of the last 100 years.

Humans are fascinated by things that scare them, such as death-defying stunts and true crime documentaries, provided these sources of fear at a safe distance. Horror movies are no different, providing a relentless villain, such as Jason in Friday the 13th or a supernatural threat.

For their study into cinematic terror, published in the journal NeuroImage, the researchers first established the 100 best and scariest horror movies of the past century, and how they made people feel.

Unseen threats are the scariest

Firstly, 72% of people report watching at last one horror movie every 6 months, and the reasons for doing so, besides the feelings of fear and anxiety, was primarily that of excitement. Watching horror movies was also an excuse to socialise, with many people preferring to watch horror movies with others than on their own.

People found horror that was psychological in nature and based on real events the scariest, and were far more scared by things that were unseen or implied rather than what they could actually see.

“This latter distinction reflects two types of fear that people experience. The creeping foreboding dread that occurs when one feels that something isn’t quite right, and the instinctive response we have to the sudden appearance of a monster that make us jump out of our skin,” says principal investigator, Professor Lauri Nummenmaa from Turku PET Centre.

MRI reveals different types of fear

Researchers wanted to know how the brain copes with fear in response to this complicated and ever changing environment. The group had people watch two horror movies (The Conjuring 2, 2016, and Insidious, 2010; both directed by James Wan) whilst measuring neural activity in a magnetic resonance imaging scanner.

During those times when anxiety is slowly increasing, regions of the brain involved in visual and auditory perception become more active, as the need to attend for cues of threat in the environment become more important. After a sudden shock, brain activity is more evident in regions involved in emotion processing, threat evaluation, and decision making, enabling a rapid response.

However, these regions are in continuous talk-back with sensory regions throughout the movie, as if the sensory regions were preparing response networks as a scary event was becoming increasingly likely.

“Therefore, our brains are continuously anticipating and preparing us for action in response to threat, and horror movies exploit this expertly to enhance our excitement,” explains Researcher Matthew Hudson.

Source: University of Turku

Categories : Metabolic DisordersTags :

Researchers Find an Obesity-related Trigger for Diabetes

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Obesity
Image source: Pixabay CC0

A new study may help explain how excess weight can contribute to diabetes, which may lead to targeted treatment and prevention. The findings suggest that many people with elevated insulin levels, an early marker of diabetes risk, also have defects in an enzyme important to the processing of a key fatty acid from the diet. The research was published in the journal Cell Metabolism.

“Between 30 million and 40 million people in the United States have Type 2 diabetes, and another 90 million to 100 million have risk factors that make them likely to develop Type 2 diabetes in the future,” said senior investigator Clay F. Semenkovich, MD, at the Washington University School of Medicine in St. Louis. “Many at risk for diabetes have elevated levels of insulin, a hallmark of insulin resistance and a signal that means trouble may be brewing. If we could intervene before they actually develop diabetes, we might be able to prevent significant health problems – such as heart disease, chronic kidney disease, nerve damage, vision loss and other problems – in a great number of people.”

When there is excessive body fat, beta cells in the pancreas ae signalled to secrete more insulin. When insulin levels become elevated and remain high, the body can become resistant to insulin, and eventually the beta cells that secrete insulin can fail, leading to diabetes.

Studying human tissue samples, Washington University researchers found that the overproduction of insulin involves a process called palmitoylation. This is the process by which cells attach the fatty acid palmitate to proteins.

Thousands of human proteins can be attached to palmitate, but the researchers found that when this fatty acid isn’t removed from proteins in beta cells, diabetes is the end result. Examining tissue samples from people who were thin or overweight, and with and without diabetes, the researchers found that the people with diabetes were deficient in an enzyme that removes palmitate from beta cells.

“They hyper-secrete insulin because this process goes awry, and they can’t appropriately regulate the release of insulin from beta cells,” Semenkovich explained. “Regulating insulin release is controlled in part by this palmitoylation process.”

The research team also genetically engineered a mouse that was deficient in the APT1 enzyme, which is responsible for palmitate removal from proteins. The engineered mice went on to develop diabetes.

Because impaired APT1 function contributed to diabetes risk, the researchers worked with the university’s Center for Drug Discovery to screen and identify compounds that can increase the activity of the APT1 enzyme.

“We’ve found several candidate drugs, and we’re pursuing those,” Semenkovich said. “We think that by increasing APT1 activity, we might reverse this process and potentially prevent people at risk from progressing to diabetes.”

Although he said the new findings identifying APT1 as a target are an important step, Semenkovich explained that APT1 is only one treatment target among many.

“There are several ways that Type 2 diabetes may develop,” he said. “This enzyme is not the answer, but it’s an answer, and it appears we have some promising tools that might keep some people with prediabetes from developing diabetes.”

Source: Washington University School of Medicine

Categories : GeneticsTags :

Why do Older Fathers Pass on More Mutations?

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Photo by Muhammad Daudy on Unsplash

It is not known exactly why older fathers pass on more mutations than younger ones do, even though the male reproductive system is a hotpot for evolution. The mechanisms that might underlie these well-documented trends have long remained a mystery. Now, a new study in the journal Nature Ecology & Evolution describes why older male fruit flies are more likely to pass mutations onto their offspring, which may hold clues for inherited-disease risk in humans.

Researchers in Li Zhao’s lab at Rockefeller University studied mutations that occur during the production of sperm from germline cells, known as spermatogenesis. They found that mutations are common in the testes of both young and old fruit flies, but more abundant in older flies from the outset. Moreover, many of these mutations seem to be removed in younger fruit flies during spermatogenesis by the body’s genomic repair mechanisms – but they fail to be fixed in the testes of older flies.

“We were trying to test whether the older germline is less efficient at mutation repair, or whether the older germline just starts out more mutated,” says first author Evan Witt. “Our results indicate that it’s actually both. At every stage of spermatogenesis, there are more mutations per RNA molecule in older flies than in younger flies.”

Genetic self-repair

Genomes have a few repair mechanisms. When it comes to testes, they have to work overtime; testes have the highest rate of gene expression of any organ. Moreover, genes that are highly expressed in spermatogenesis tend to have fewer mutations than those that are not. This sounds counterintuitive, but it makes sense: One theory to explain why the testes express so many genes holds that it might be a sort of genomic surveillance mechanism – a way to reveal, and then weed out, problematic mutations.

But when it comes to older sperm, the researchers found, the weed-whacker apparently sputters out. Previous research suggests that a faulty transcription-coupled repair mechanism, which only fixes transcribed genes, could be to blame.

Inherited or new mutations?

To get these results, scientists in the Laboratory of Evolutionary Genetics and Genomics did single-cell sequencing on the RNA from the testes of about 300 fruit flies, roughly half of them young (48 hours old) and half old (25 days old), advancing a line of inquiry they began in 2019. In order to understand whether the mutations they detected were somatic, or inherited from the flies’ parents, or de novo they then sequenced the genome of each fly. They were able to document that each mutation was a true original. “We can directly say this mutation was not present in the DNA of that same fly in its somatic cells,” says Witt. “We know that it’s a de novo mutation.”

This unconventional approach – inferring genomic mutations from single-cell RNA sequencing and then comparing them to the genomic data – allowed the researchers to match mutations to the cell type in which they occurred. “It’s a good way to compare mutational load between cell types, because you can follow them throughout spermatogenesis,” Witt says.

Applicability to humans

The next step is to expand the analysis to more age groups of flies and test whether or not this transcription repair mechanism can occur – and if it does, identify the pathways responsible, Witt says. “What genes,” he wonders, “are really driving the difference between old and young flies in terms of mutation repair?”

Because fruit flies have a high reproductive rate, investigating their mutation patterns can offer new insights into the effect of new mutations in human health and evolution, says Zhao.

Witt adds, “It’s largely unknown whether a more mutated male germline is more or less fertile than a less mutated one. There’s not been very much research on it except for at a population level. And if people inherit more mutations from ageing fathers, that increases the odds of de novo genetic disorders or certain types of cancers.”

Source:

Categories : Pain ManagementTags :

Brain Structures Predict Risk of Awareness under Anaesthesia

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Photo by Anna Shvets on Pexels

Awareness during anaesthesia is an extremely rare but horrific risk for patients. Now, for the first time, neuroscientists have identified brain structures which could predict an individual’s predisposition this phenomenon. The findings, just published in the journal Human Brain Mapping, could help identify patients who need larger anaesthetic doses.

Although anaesthesia has been used in clinical medicine for over 150 years, scientists do not fully understand why its effect on people is so varied. One in four patients presumed to be unconscious during general anaesthesia may in fact have subjective experiences, such as dreaming. Estimated to occur in 1:1000 to 1:20 000 cases, some patients may have awareness under general anaesthetic. These experiences may range from hearing sounds to the pain of surgery combined with the sensation of suffocation and paralysis in the setting of neuromuscular blockade.

The researchers from Trinity College Dublin found that one in three participants were unaffected by moderate propofol sedation in their response times, thus thwarting a key aim of anaesthesia – the suppression of behavioural responsiveness.

The research also showed, for the first time, that the participants who were resistant to anaesthesia had fundamental differences in the function and structures of the fronto-parietal regions of the brain to those who remained fully unconscious. Crucially, these brain differences could be predicted prior to sedation.

Lorina Naci, Associate Professor of Psychology, Trinity who lead the research said:

“The detection of a person’s responsiveness to anaesthesia prior to sedation has important implications for patient safety and wellbeing. Our results highlight new markers for improving the monitoring of awareness during clinical anaesthesia. Although rare, accidental awareness during an operation can be very traumatic and lead to negative long-term health outcomes, such as post-traumatic stress disorder, as well as clinical depression or phobias.”

“Our results suggest that individuals with larger grey matter volume in the frontal regions and stronger functional connectivity within fronto-parietal brain networks, may require higher doses of propofol to become nonresponsive compared to individuals with weaker connectivity and smaller grey matter volume in these regions.”

The research, conducted in Ireland and Canada, investigated 17 healthy individuals who were sedated with propofol, the most common clinical anaesthetic agent. The participants’ response time to detect a simple sound was measured when they were awake and as they became sedated. Brain activity of 25 participants as they listened to a simple story in both states was also measured.

Source: Trinity College Dublin

Categories : Mental HealthTags :

Even Placebos Given Openly can Reduce Feelings of Guilt

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Photo by Caleb Woods on Unsplash

While guilt is usually an appropriate emotional reaction, usually in response to doing something negative or hurtful, sometimes it can be unwarranted and persistent. Researchers at the University of Basel have shown that placebos can help assuage feelings of guilt, even when the placebo is administered openly, ie the participants are aware of the treatment being a placebo.

Guilt is considered an important moral emotion, as long as it is adaptive – in other words, appropriate and in proportion to the situation. “It can improve interpersonal relationships and is therefore valuable for social cohesion,” says Dilan Sezer, researcher at the Division of Clinical Psychology and Psychotherapy at the University of Basel. Previous research had demonstrated that placebos – even given openly – can still be effective in provoking a beneficial response.

In order to arouse feelings of guilt, healthy participants were recruited and asked to write about a time when they had disregarded important rules of conduct, or treated someone close to them unfairly, hurt or even harmed them. The idea was that the study participants should still feel bad about the chosen situation.

Participants were then randomised to three conditions: Participants in one group received placebo pills with being deceptively told that this was a real medication while participants in another group were told that they are given a placebo. Both groups were told that what they had been given will be effective against feelings of guilt. The control group received no treatment at all. The results, published in Scientific Reports, showed that feelings of guilt were significantly reduced in both placebo groups compared with those without medication.

This was also the case when the subjects knew they had been given a placebo.  “Our study therefore supports the intriguing finding that placebos work even when they are administered openly, and that explanation of the treatment is key to its effectiveness,” states the study’s lead author, Dilan Sezer.

Where feelings of guilt are irrational and continue for longer periods of time, they are considered maladaptive – in other words, disproportionate. These emotions can affect people’s health and are also, among other things, a common symptom of depression.

Scientific studies have shown that placebo effects can be powerful in treating depression. But the finding that open-label placebos can also be useful for such strong emotions as guilt is new. It stands to reason, says Dilan Sezer, that we should try to harness these effects to help those affected. “The administering of open-label placebos, in particular, is a promising approach, as it preserves patient autonomy by allowing patients to be fully aware of how the intervention works.” The results of the study are an initial promising step in the direction of symptom-specific and more ethical treatments for psychological complaints using open-label placebos, Sezer continues.

Further research will need to be done into whether it is possible to treat maladaptive guilt with placebos. And it is still not known whether similar effects are also possible with other feeling states. For Dilan Sezer, one thing is certain: “Using open-label placebos would be an inexpensive and straightforward treatment option for many psychological and physical complaints.”

Source: University of Basel