Researchers Want to Restore ‘Good Noise’ in Older Brains

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to listen to A brain, one of the best tools neuroscientists have is an fMRI scan, which helps to map blood flow, and therefore the spikes in oxygen that occur when a particular brain region is being used. It reveals a noisy world. Blood oxygen levels change from moment to moment, but those spikes never completely level off. “Your brain, even when at rest, is not going to be completely silent,” says Purta Lalwani, a PhD student in cognitive neuroscience at the University of Michigan. She imagines the brain, even at its most calm, as a tennis player waiting to return to a serve: “He’s not going to stand still. He’s going to back off a little. Getting ready to hit the backhand.”

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Many fMRI studies filter out the noise that researchers want to examine in order to find particular spikes. But for Lalwani, that noise is the most telling signal. For him, this is a sign of cognitive flexibility. Blood oxygen levels in a young, healthy brain have signs of extreme variability from time to time. Older people differ less, at least in certain areas of the brain.

Nearly a decade ago, scientists showed for the first time the link between reduced neural signal variability and cognitive decline with healthy aging rather than typical dementia. Brain noise is a concrete proxy for details that are more abstract, says Lalwani: “How efficient is the information transfer, how well the neural networks are connected, how well the underlying neural network is functioning in general.” “

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but Why What changes with age has been a mystery. So the question is whether it is reversible.

In result published in November Journal of NeuroscienceIn this study, Lalwani’s team showed that a small dose of lorazepam, an anti-anxiety drug, could reverse the decline in signal variability, at least momentarily. The drug dials down inhibitory messages in the brain but makes it more dynamic, ready to respond and respond quickly. In the study, brain signals from older participants, who had previously performed poorly on cognitive tasks, returned to noise levels that looked more like those of younger ones.

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“Ten or so years ago, most people thought variability in the brain was a bad thing,” says Cheryl Grady, a cognitive neuroscientist at the Rotman Research Institute who has studied brain signal variability but was not involved in Lalvani’s study. Were. But now, he thinks, more people realize the potential of this new metric. “I’m in favor of this whole approach.”

Around 2008, researchers It began to be suspected that the so-called noise in the fMRI signals had a deeper meaning. By 2010, Douglas Garrett, then a PhD student, had shown that Variability in Blood Oxygen fMRI Signals Those readings predicted a person’s age better than the size of the spikes. His hunch was that the standard deviation—a measure of how similar or different signals are in a raw dataset—could tell stories that just an average of spike size could not.

Time And Time Again, he and his colleagues show a strong association between this “noise,” age and cognitive processing speed. When you perform cognitive tasks, such as quickly selecting two matching images, your brain’s signals become more variable. But in 2012, Garrett showed that young people experience significantly greater variability than older people when performing a matching task. And in 2017, his team proved that age-related changes in variability are not some result of individual differences in blood flow.

variability frequent beats of those blood oxygen level signals Average Signal size as the best predictor of cognitive decline. “Same task, same subject, same data,” he says. “He won that race, and continues to win that race, every time we have.” Garrett, now a senior scientist at the Max Planck Institute for Human Development, co-authored the new paper with Lalwani.

The notion – that noise could be a signal – was not always well received. “People were really thinking about it just as well” Nonsense,” says Greg Samnez-Larkin, a cognitive neuroscientist at Duke University who was not involved in the study. (He joined the study of signal variability as a graduate student around the same time as Garrett.) his own experimentsIn this study, they studied the relationship between this noise level and the likelihood of older adults making worse financial decisions.

In their new work, the team focused on the brain chemical that controls this change in neural noise levels. The neurotransmitter GABA seemed like an obvious target. GABA is a small molecule, about twice as heavy as a molecule of carbon dioxide. Yet it plays a big role as a primary inhibitor of brain damage. When molecular receptors in neurons come across GABA, they are less likely to fire. Too little GABA can over-stimulate the brain. Too much… well, that’s how anesthesia works. GABA is the wet blanket that balances the brain’s party, and its concentration drop In the mind of aging.

Lalwani’s team recruited 25 young adults (between 18 and 25 years old) and 21 older people (aged 65 to 85) for the fMRI study. Before being scanned, each person completed seven tasks designed to test cognition. One asked them to match the images by size or color, or as quickly as possible, to find out whether the two images were different. The other tested his ability to read aloud. Still another asked them to remember pictures of animals they saw on an iPad, then listed them in order of size. The tasks gave Lalwani’s team an objective way to classify the participants’ general cognitive levels.

Then, each person underwent two fMRI scanning sessions during which they rested quietly while a snapshot of their brain blood oxygen levels was collected every two seconds. For one scan, the team gave each person a low dose of lorazepam, a benzodiazepine known to enhance the effects of GABA. For another, everyone took a placebo that had no effect. (The sequence of each session was random, so participants did not know which pill they had taken first.)

The placebo sessions revealed a familiar story: Older participants showed less brain signal variability in their resting state, particularly in the frontal regions of the brain responsible for memory and language, and other processing associated with sight, sound and touch. . But would the researchers notice any difference during the lorazepam sessions?

Lalwani remembers waiting for his computer to churn through a vast data set of brain images. “I was watching the progress bar go by,” she recalls. is waiting. wait more. Then, his answer loaded up: Yes, people had greater signal variability while taking lorazepam. And even better, she could see who had the biggest change: those who performed the worst on cognitive test tasks. “They were the ones who needed it the most. They were the ones to get it,” says Lalwani. “It is rare to see effects like these.”

make up mind more The barrier made it more dynamic. “You can imagine that it’s kind of counterintuitive. Shouldn’t that shut down the whole thing?” Garrett says. “But that’s not really how the brain is made.”

Neural networks stay agile by finding the right balance between inhibition and stimulation. If the effect of GABA is too small and the inhibition is too weak, the brain becomes overstimulated—neurons fire unnecessarily, and the network collapses into a very stable So that he can’t move easily. Increasing the inhibitory effect of GABA shifts the brain to a less excitable, more flexible state. Changes in the brain’s GABA levels have been reported before has been shown to help Against some of the symptoms of Alzheimer’s, such as brain cell death and memory loss.

But while studies show that the brain does indeed make noise, and noise is associated with better cognitive performance, Samnez-Larkin points out that the work is missing an important piece of evidence: evidence that a GABA-enhancer. The drug actually improves cognition. The team did not show that lorazepam outperformed those who performed poorly in later tests, or did not show how long the changes in brain noise levels lasted. It is also unclear whether the drug affects the parts of the brain that need a boost in order to perform optimally. The effect of lorazepam is diffuse. “It’s not like it goes to a specific part of the brain,” Samnez-Larkin says. “You can basically help some parts of the brain but overdose other parts of the brain.” The drug tested for real-world treatment needs to be more specific in its action than lorazepam.

In fact, Lalwani estimates that subjects can actually perform Worse Side effects after taking lorazepam because GABA levels increase throughout the brain include drowsiness and memory loss. “It doesn’t mean that people should take GABA pills,” says Lalwani.

That said, targeting the GABA pathway doesn’t have to mean popping pills. Daily aerobic exercise can also increase those levels, and increase signal variability, according to Aga Burzynska, a cognitive neuroscientist at Colorado State University who was not involved in the work. ,[Lalwani’s study] really opens up another avenue for studying the causes of cognitive decline — or what the ‘players’ are.” Burzynska says. She’s particularly interested in how this helps us better treat healthy aging. More than 50 million Americans are 65 or older. Most will never be diagnosed with cognitive dysfunction, but they can still deal with a general decline. “It’s a loss of independence and everyday life.” The main reason is,” she says. “There’s so much to win.”

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