Tag: memory

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These Newly Discovered Brain Cells Enable us to Remember Objects

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Discovery of ‘ovoid cells’ reshapes our understanding of how memory works, and could open the door to new treatments for Alzheimer’s disease, epilepsy and more.

Ovoid cells. Photo credit: Dr. Mark Cembrowski

Take a look around your home and you’ll find yourself surrounded by familiar comforts – photos of family and friends on the wall, well-worn tekkies by the door, a shelf adorned with travel mementos.

Objects like these are etched into our memory, shaping who we are and helping us navigate environments and daily life with ease. But how do these memories form? And what if we could stop them from slipping away under a devastating condition like Alzheimer’s disease?

Scientists at the University of British Columbia have just uncovered a crucial piece of the puzzle. In a study published in Nature Communications, the researchers have discovered a new type of brain cell that plays a central role in our ability to remember and recognise objects. 

Called ‘ovoid cells,’ these highly-specialised neurons activate each time we encounter something new, triggering a process that stores those objects in memory and allowing us to recognise them months, even years, later.

“Object recognition memory is central to our identity and how we interact with the world,” said Dr Mark Cembrowski, the study’s senior author, and an associate professor of cellular and physiological sciences at UBC and investigator at the Djavad Mowafaghian Centre for Brain Health. “Knowing if an object is familiar or new can determine everything from survival to day-to-day functioning, and has huge implications for memory-related diseases and disorders.”

Hiding in plain sight

Named for the distinct egg-like shape of their cell body, ovoid cells are present in relatively small numbers within the hippocampus of humans, mice and other animals.

Adrienne Kinman, a PhD student in Dr Cembrowski’s lab and the study’s lead author, discovered the cells’ unique properties while analysing a mouse brain sample, when she noticed a small cluster of neurons with highly distinctive gene expression.

“They were hiding right there in plain sight,” said Kinman. “And with further analysis, we saw that they are quite distinct from other neurons at a cellular and functional level, and in terms of their neural circuitry.”

To understand the role ovoid cells play, Kinman manipulated the cells in mice so they would glow when active inside the brain. The team then used a miniature single-photon microscope to observe the cells as the mice interacted with their environment.

The ovoid cells lit up when the mice encountered an unfamiliar object, but as they grew used to it, the cells stopped responding. In other words, the cells had done their jobs: the mice now remembered the objects.

“What’s remarkable is how vividly these cells react when exposed to something new. It’s rare to witness such a clear link between cell activity and behaviour,” said Kinman. “And in mice, the cells can remember a single encounter with an object for months, which is an extraordinary level of sustained memory for these animals.”

New insights for Alzheimer’s disease, epilepsy

The researchers are now investigating the role that ovoid cells play in a range of brain disorders. The team’s hypothesis is that when the cells become dysregulated, either too active or not active enough, they could be driving the symptoms of conditions like Alzheimer’s disease and epilepsy.

“Recognition memory is one of the hallmarks of Alzheimer’s disease – you forget what keys are, or that photo of a person you love. What if we could manipulate these cells to prevent or reverse that?” said Kinman. “And with epilepsy, we’re seeing that ovoid cells are hyperexcitable and could be playing a role in seizure initiation and propagation, making them a promising target for novel treatments.”

For Dr Cembrowski, discovering the highly specialised neuron upends decades of conventional thinking that the hippocampus contained only a single type of cell that controlled multiple aspects of memory.

“From a fundamental neuroscience perspective, it really transforms our understanding of how memory works,” he said. “It opens the door to the idea that there may be other undiscovered neuron types within the brain, each with specialised roles in learning, memory and cognition. That creates a world of possibilities that would completely reshape how we approach and treat brain health and disease.”

Source: University of British Columbia

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The Surprising Link between Muscle Signalling and Brain Memory

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New research shows that how a network of subcellular structures is responsible for transmitting signals in neurons. This movie shows 3D renderings of these structures in high-resolution 3D electron microscopy images of fruit fly neurons. The endoplasmic reticulum (green), plasma membrane (blue), mitochondria (pink), microtubules (tan), and ER-plasma membrane contacts (magenta) are segmented from FIB-SEM datasets of a Drosophila melanogaster MBON1 neuron. Credit: Benedetti et al.

New research led by the Lippincott-Schwartz Lab shows that a network of subcellular structures similar to those responsible for propagating molecular signals that make muscles contract are also responsible for transmitting signals in the brain that may facilitate learning and memory.

“Einstein said that when he uses his brain, it is like he is using a muscle, and in that respect, there is some parallel here,” says Janelia Senior Group Leader Jennifer Lippincott-Schwartz. “The same machinery is operating in both cases but with different readouts.” The research appears in the journal Cell.

The first clue about the possible connection between brain and muscle cells came when Janelia scientists noticed something strange about the endoplasmic reticulum, or ER – the membranous sheets and folds inside cells that are crucial for many cellular functions.

Research scientist Lorena Benedetti was tracking molecules at high resolution along the surface of the ER in mammalian neurons when she saw that the molecules were tracing a repeating, ladder-like pattern along the entire length of the dendrites.

Around the same time, Senior Group Leader Stephan Saalfeld alerted Lippincott-Schwartz to high-resolution 3D electron microscopy images of neurons in the fly brain where the ER was also forming regularly spaced, transversal structures.

This movie shows time-lapse high-resolution imaging in neurons, revealing the dynamic behavior of ER tubules contrasted with the persistence of ER-PM junctional sites over time. Time-lapse acquired using 2D lattice-SIM in burst mode of HaloTag-Sec61β (labeled with JF585 HaloTag-ligand) expressing neurons. Scale bars: 0.5 μm. Credit: Benedetti et al.

The ER normally appears like a huge, dynamic net, so as soon as Lippincott-Schwartz saw the structures, she knew her lab needed to figure out what they were for.

“In science, structure is function,” says Lippincott-Schwartz, who also heads Janelia’s 4D Cellular Physiology research area. “This is an unusual, beautiful structure that we are seeing throughout the whole dendrite, so we just had this feeling that it must have some important function.”

The researchers, led by Benedetti, started by looking at the only other area of the body known to have similar, ladder-like ER structures: muscle tissue. In muscle cells, the ER and the plasma membrane – the outer membrane of the cell – meet at periodic contact sites, an arrangement controlled by a molecule called junctophilin.

Using high-resolution imaging, the researchers discovered that dendrites also contain a form of junctophilin that controls contact sites between their ER and plasma membrane. Further, the team found that the same molecular machinery controlling calcium release at muscle cells’ contact sites – where calcium drives muscle contraction – was also present at dendrite contact sites – where calcium regulates neuronal signalling.

Because of these clues, the researchers had a hunch that the molecular machinery at the dendritic contact sites must also be important for transmitting calcium signals, which cells use to communicate. They suspected that the contact sites along the dendrites might act like a repeater on a telegraph machine: receiving, amplifying, and propagating signals over long distances. In neurons, this could explain how signals received at specific sites on dendrites are relayed to the cell body hundreds of micrometres away.  

“How that information travels over long distances and how the calcium signal gets specifically amplified was not known,” says Benedetti. “We thought that ER could play that role, and that these regularly distributed contact sites are spatially and temporally localised amplifiers: they can receive this calcium signal, locally amplify this calcium signal, and relay this calcium signal over a distance.”

The researchers found that this process is triggered when a neuronal signal causes calcium to enter the dendrite through voltage-gated ion channel proteins, which are positioned at the contact sites. Although this initial calcium signal dissipates quickly, it triggers the release of additional calcium from the ER at the contact site.

Source: Howard Hughes Medical Institute

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Memories are Stored in Cells Outside the Brain, Too

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It’s common knowledge that the neurons in the brain store memories. But a team of scientists has discovered that cells from other parts of the body also perform a memory function, opening new pathways for understanding how memory works and creating the potential to enhance learning and to treat memory-related afflictions. 

“Learning and memory are generally associated with brains and brain cells alone, but our study shows that other cells in the body can learn and form memories, too,” explains New York University’s Nikolay V. Kukushkin, the lead author of the study in Nature Communications. 

The research sought to better understand if non-brain cells help with memory by borrowing from a long-established neurological property – the massed-spaced effect – which shows that we tend to retain information better when studied in spaced intervals rather than in a single, intensive session – better known as cramming for a test.

In the Nature Communications research, the scientists replicated learning over time by studying two types of non-brain human cells in a laboratory (one from nerve tissue and one from kidney tissue) and exposing them to different patterns of chemical signals – just like brain cells are exposed to patterns of neurotransmitters when we learn new information. In response, the non-brain cells turned on a “memory gene” – the same gene that brain cells turn on when they detect a pattern in the information and restructure their connections in order to form memories.

“Learning and memory are generally associated with brains and brain cells alone, but our study shows that other cells in the body can learn and form memories, too.”

NYU’s Nikolay Kukushkin 

To monitor the memory and learning process, the scientists engineered these non-brain cells to make a glowing protein, which indicated when the memory gene was on and when it was off.

The results showed that these cells could determine when the chemical pulses, which imitated bursts of neurotransmitter in the brain, were repeated rather than simply prolonged – just as neurons in our brain can register when we learn with breaks rather than cramming all the material in one sitting. Specifically, when the pulses were delivered in spaced-out intervals, they turned on the “memory gene” more strongly, and for a longer time, than when the same treatment was delivered all at once.

“This reflects the massed-space effect in action,” says Kukushkin, a clinical associate professor of life science at NYU Liberal Studies and a research fellow at NYU’s Center for Neural Science. “It shows that the ability to learn from spaced repetition isn’t unique to brain cells, but, in fact, might be a fundamental property of all cells.”

The researchers add that the findings not only offer new ways to study memory, but also point to potential health-related gains.

“This discovery opens new doors for understanding how memory works and could lead to better ways to enhance learning and treat memory problems,” observes Kukushkin. “At the same time, it suggests that in the future, we will need to treat our body more like the brain – for example, consider what our pancreas remembers about the pattern of our past meals to maintain healthy levels of blood glucose or consider what a cancer cell remembers about the pattern of chemotherapy.”

Source: New York University

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Pulling Back the Curtain on the Brain Circuit for Memory Recall

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Photo by Anna Shvets

Deep within either hemisphere of the brain is the “claustrum complex”, which contributes to consciousness and awareness. Many diseases known to be related to higher cognitive function, such as Alzheimer’s, schizophrenia, and ADD/ADHD, are also closely linked to abnormal function of this particular part of the brain. But how the different parts of the claustrum complex work or how its circuits and communication system are organised is not fully understood.

Researchers at Aarhus University have now uncovered this, and their results identify, down to the cellular level, which part of the claustrum complex controls our ability to discriminate familiar and novel things.

“Our study focuses on an area of the claustrum called the ‘endopiriform,’ which is a relatively unknown brain structure despite its unique brain network and cellular properties,” explains Asami Tanimura, an associate professor and the lead researcher of the study appearing as a preprint in eLife.

“For the first time, we have dissected the circuit of endopiriform to the hippocampus, and demonstrated how this pathway is crucial for recognition memory.”

In mouse models, researchers were able to observe how the mice’s behaviour changed when they respectively ‘turned on’ and ‘turned off’ the activity in this specific cell group.

Asami explains: “We observed that the cells in the endopiriform were active when the mice interacted with new conspecifics or objects, and when we inhibited this cell group, it reduced the mice’s ability to distinguish novel mouse or object from familiar ones.”

Based on this, the researchers concluded that this specific cell group in the claustrum seems to play a key role in sending memory-guided attention signal to the hippocampus.

“This is entirely new knowledge about this small but important part of the brain, and it gives us a unique understanding of the special circuit involved in recognition memory,” explains Asami.

What this knowledge might mean, and whether it could lead to the development of new treatment methods targeted at disorders in this part of the brain, remains to be seen. However, Asami and her colleagues are optimistic:

“To develop effective treatment methods, a very detailed understanding of the cells’ circuits is required. With our study, we have at least opened a door that has previously been closed in terms of specific role of the endopiriform-hippocampal circuit on higher cognitive function.”

Source: Aarhus University

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How the Brain’s Working Memory… Works

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Photo by Alex Green on Unsplash

Cedars-Sinai investigators have discovered how brain cells responsible for working memory – which holds onto things like phone numbers while we use them – coordinate intentional focus and short-term storage of information. Their discovery, which confirms the involvement of the hippocampus, is published in the journal Nature.

“We have identified for the first time a group of neurons, influenced by two types of brain waves, that coordinate cognitive control and the storage of sensory information in working memory,” said Jonathan Daume, PhD, a postdoctoral scholar in the Rutishauser Lab at Cedars-Sinai and first author of the study. “These neurons don’t contain or store information, but are crucial to the storage of short-term memories.”

Working memory, which requires the brain to store information for only seconds, is fragile and requires continued focus to be maintained, explained senior study author Ueli Rutishauser, PhD, director of the Center for Neural Science and Medicine at Cedars-Sinai. It can be affected by different diseases and conditions.

“In disorders such as Alzheimer’s disease or attention-deficit hyperactivity disorder, it is often not memory storage, but rather the ability to focus on and retain a memory once it is formed that is the problem,” said Rutishauser, who is a professor of Neurosurgery, Neurology and Biomedical Sciences at Cedars-Sinai. “We believe that understanding the control aspect of working memory will be fundamental for developing new treatments for these and other neurological conditions.”

To explore how working memory functions, investigators recorded the brain activity of 36 hospitalised patients who had electrodes surgically implanted in their brains as part of an epilepsy diagnosis procedure. The team recorded the activity of individual brain cells and brain waves while the patients performed a task that required use of working memory.

On a computer screen, patients were shown either a single photo or a series of three photos of various people, animals, objects or landscapes. Next, the screen went blank for just under three seconds, requiring patients to remember the photos they just saw. They were then shown another photo and asked to decide whether it was the one (or one of the three) they had seen before.

When patients performing the working memory task were able to respond quickly and accurately, investigators noted the firing of two groups of neurons: “category” neurons that fire in response to one of the categories shown in the photos, such as animals, and “phase-amplitude coupling,” or PAC, neurons.

PAC neurons, newly identified in this study, don’t hold any content, but use a process called phase-amplitude coupling to ensure the category neurons focus and store the content they have acquired. PAC neurons fire in time with the brain’s theta waves, which are associated with focus and control, as well as to gamma waves, which are linked to information processing. This allows them to coordinate their activity with category neurons, which also fire in time to the brain’s gamma waves, enhancing patients’ ability to recall information stored in working memory.

“Imagine when the patient sees a photo of a dog, their category neurons start firing ‘dog, dog, dog’ while the PAC neurons are firing ‘focus/remember,'” Rutishauser said. “Through phase-amplitude coupling, the two groups of neurons create a harmony superimposing their messages, resulting in ‘remember dog.’ It is a situation where the whole is greater than the sum of its parts, like hearing the musicians in an orchestra play together. The conductor, much like the PAC neurons, coordinates the various players to act in harmony.”

PAC neurons do this work in the hippocampus, a part of the brain that has long been known to be important for long-term memory. This study offers the first confirmation that the hippocampus also plays a role in controlling working memory, Rutishauser said.

Source: Cedars-Sinai Medical Center

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Making Long-term Memories Requires DNA Damage and Brain Inflammation

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Just as you can’t make an omelette without breaking eggs, scientists at Albert Einstein College of Medicine have found that you can’t make long-term memories without DNA damage and inflammation in the brain. Their surprising findings were published online today in the journal Nature.

“Inflammation of brain neurons is usually considered to be a bad thing, since it can lead to neurological problems such as Alzheimer’s and Parkinson’s disease,” said study leader Jelena Radulovic, MD, PhD, professor of psychiatry and behavioural sciences at Einstein. “But our findings suggest that inflammation in certain neurons in the brain’s hippocampal region is essential for making long-lasting memories.”

The hippocampus has long been known as the brain’s memory centre. Dr Radulovic and her colleagues found that a stimulus sets off a cycle of DNA damage and repair within certain hippocampal neurons that leads to stable memory assemblies, ie clusters of brain cells representing past experiences.

From shocks to stable memories

The researchers discovered this memory-forming mechanism by giving mice brief, mild shocks sufficient to form an episodic memory of the shock event. Then, they analysed neurons in the hippocampal region and found that genes participating in an important inflammatory signalling pathway had been activated.

“We observed strong activation of genes involved in the Toll-Like Receptor 9 (TLR9) pathway,” said Dr Radulovic, who is also director of the Psychiatry Research Institute at Montefiore Einstein (PRIME). “This inflammatory pathway is best known for triggering immune responses by detecting small fragments of pathogen DNA. So at first we assumed the TLR9 pathway was activated because the mice had an infection. But looking more closely, we found, to our surprise, that TLR9 was activated only in clusters of hippocampal cells that showed DNA damage.”

Brain activity routinely induces small breaks in DNA that are repaired within minutes. But in this population of hippocampal neurons, the DNA damage appeared to be more substantial and sustained.

Triggering inflammation to make memories

Further analysis showed that DNA fragments, along with other molecules resulting from the DNA damage, were released from the nucleus, after which the neurons’ TLR9 inflammatory pathway was activated; this pathway in turn stimulated DNA repair complexes to form at an unusual location: the centrosomes. These organelles are present in the cytoplasm of most animal cells and are essential for coordinating cell division. But in neurons – which don’t divide – the stimulated centrosomes participated in cycles of DNA repair that appeared to organise individual neurons into memory assemblies.

“Cell division and the immune response have been highly conserved in animal life over millions of years, enabling life to continue while providing protection from foreign pathogens,” Dr. Radulovic said. “It seems likely that over the course of evolution, hippocampal neurons have adopted this immune-based memory mechanism by combining the immune response’s DNA-sensing TLR9 pathway with a DNA repair centrosome function to form memories without progressing to cell division.”

Resisting inputs of extraneous information

During the week required to complete the inflammatory process, the mouse memory-encoding neurons were found to have changed in various ways, including becoming more resistant to new or similar environmental stimuli. “This is noteworthy,” said Dr Radulovic, “because we’re constantly flooded by information, and the neurons that encode memories need to preserve the information they’ve already acquired and not be ‘distracted’ by new inputs.”

“This is noteworthy,” said Dr Radulovic, “because we’re constantly flooded by information, and the neurons that encode memories need to preserve the information they’ve already acquired and not be ‘distracted’ by new inputs.”

Importantly, the researchers found that blocking the TLR9 inflammatory pathway in hippocampal neurons not only prevented mice from forming long-term memories but also caused profound genomic instability, ie, a high frequency of DNA damage in these neurons.

“Genomic instability is considered a hallmark of accelerated aging as well as cancer and psychiatric and neurodegenerative disorders such as Alzheimer’s,” Dr Radulovic said.

“Drugs that inhibit the TLR9 pathway have been proposed for relieving the symptoms of long COVID. But caution needs to be shown because fully inhibiting the TLR9 pathway may pose significant health risks.”

PhD Student Elizabeth Wood and Ana Cicvaric, a postdoc in the Radulovic lab, were the study’s first authors at Einstein.

Source: Albert Einstein College of Medicine

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New Neural Prosthetic Device Can Help Restore Memory in Humans

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Scientists have demonstrated the first successful use of a neural prosthetic device to recall specific memories. The findings appear online in Frontiers in Computational Neuroscience.

This groundbreaking research was derived from a 2018 study led by Robert Hampson, PhD, professor of regenerative medicine, translational neuroscience and neurology at Wake Forest University School of Medicine. That study demonstrated the successful implementation of a prosthetic system that uses a person’s own memory patterns to facilitate the brain’s ability to encode and recall memory, improving recall by as much as 37%.

In the previous study, the team’s electronic prosthetic system was based on a multi-input multi-output (MIMO) nonlinear mathematical model, and the researchers influenced the firing patterns of multiple neurons in the hippocampus, a part of the brain involved in making new memories.

In this study, researchers from Wake Forest and University of Southern California (USC) built a new model of processes that assists the hippocampus in helping people remember specific information.

When the brain tries to store or recall information such as, “I turned off the stove” or “Where did I put my car keys?” groups of cells work together in neural ensembles that activate so that the information is stored or recalled.

Using recordings of the activity of these brain cells, the researchers created a memory decoding model (MDM) which let them decode what neural activity is used to store different pieces of specific information.

The neural activity decoded by the MDM was then used to create a pattern, or code, which was used to apply neurostimulation to the hippocampus when the brain was trying to store that information.

“Here, we not only highlight an innovative technique for neurostimulation to enhance memory, but we also demonstrate that stimulating memory isn’t just limited to a general approach but can also be applied to specific information that is critical to a person,” said Brent Roeder, Ph.D., a research fellow in the department of translational neuroscience at Wake Forest University School of Medicine and the study’s corresponding author.

The team enrolled 14 adults with epilepsy who were participating in a diagnostic brain-mapping procedure that used surgically implanted electrodes placed in various parts of the brain to pinpoint the origin of their seizures.

Participants underwent all surgical procedures, post-operative monitoring and neurocognitive testing at one of the three sites participating in this study including Atrium Health Wake Forest Baptist Medical Center, Keck Hospital of USC in Los Angeles and Rancho Los Amigo National Rehabilitation Center in Downey, California.

The team delivered MDM electrical stimulation during visual recognition memory tasks to see if the stimulation could help people remember images better.

They found that when they used this electrical stimulation, there were significant changes in how well people remembered things. In about 22% of cases, there was a noticeable difference in performance.

When they looked specifically at participants with impaired memory function, who were given the stimulation on both sides of their brain, almost 40% of them showed significant changes in memory performance.

“Our goal is to create an intervention that can restore memory function that’s lost because of Alzheimer’s disease, stroke or head injury,” Roeder said.

“We found the most pronounced change occurred in people who had impaired memory.”

Roeder said he hopes the technology can be refined to help people live independently by helping them recall critical information such as whether medication has been taken or whether a door is locked.

“While much more research is needed, we know that MDM-based stimulation has the potential to be used to significantly modify memory,” Roeder said.

Source: Atrium Health Wake Forest Baptist

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Magnetic Stimulation may Ameliorate Memory Deficits in Schizophrenia

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Photo by Alex Green on Pexels

Schizophrenia is often accompanied by extensive impairment of memory, including prospective memory, which is the ability to remember to perform future activities. In a randomised clinical trial published in Neuropsychopharmacology Reports, researchers found that repetitive transcranial magnetic stimulation (rTMS), a non-invasive method that uses alternating magnetic fields to induce an electric current in the underlying brain tissue, may help ameliorate certain aspects of prospective memory in individuals with schizophrenia.

The trial included 50 patients with schizophrenia and 18 healthy controls. Of the 50 patients, 26 completed active rTMS and 24 completed a sham rTMS. Healthy controls received no treatment.

Investigators assessed event-based prospective memory, which is remembering to perform an action when an external event occurs, such as remembering to give a message to a friend when you next see them and also time-based prospective memory, which is remembering to perform an action at a certain time, such as remembering to attend a scheduled meeting.

Both event-based prospective memory and time-based prospective memory scores at the baseline of the trial were significantly lower in patients with schizophrenia than in controls. After rTMS treatments, the scores of event-based prospective memories in patients were significantly improved and were similar to those in controls, while patients’ scores of time-based prospective memory did not improve.

“The findings of this study may provide one therapeutic option for prospective memory in patients with schizophrenia,” said co–corresponding author Su-Xia Li, MD, PhD, of Peking University, in China.

Source: Wiley

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The Vascular System also Plays a Role in Forming Memories

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Diagram of a capillary. Source: Wikimedia Commons

Research on long-term memories has largely focused on the role of neurons but in recent years, research is revealing that other cell types are also vital in memory formation and storage. A new study reveals the crucial role of vascular system cells (pericytes) in the formation of long-term memories of life events – memories that are lost in diseases such as Alzheimer’s. The research, published in the journal Neuron, shows that pericytes, which wrap around the capillaries work in concert with neurons to help ensure that long-term memories are formed.

Pericytes help maintain the structural integrity of the capillaries. Specifically, they control the amount of blood flowing in the brain and play a key role in maintaining the barrier that stops pathogens and toxic substances from leaking out of the capillaries and into brain tissue.

“We now have a firmer understanding of the cellular mechanisms that allow memories to be both formed and stored,” says Cristina Alberini, a professor in New York University’s Center for Neural Science and the paper’s senior author. “It’s important because understanding the cooperation among different cell types will help us advance therapeutics aimed at addressing memory-related afflictions.”

“This work connects important dots between the newly discovered function of pericytes in memory and previous studies showing that pericytes are either lost or malfunction in several neurodegenerative diseases, including Alzheimer’s disease and other dementia,” explains author Benjamin Bessières, a postdoctoral researcher in NYU’s Center for Neural Science.

The discovery, reported in the new Neuron article, of the pericytes’ significance in long-term memory emerged because Alberini, Bessières, Kiran Pandey, and their colleagues examined the role of insulin-like growth factor 2 (IGF2) – a protein that was known to increase following learning in brain regions, such as the hippocampus, and to play a critical role in the formation and storage of memories.

They found that IGF2’s highest levels in the brain cells of the hippocampus do not come from neurons or glial cells, or other vascular cells, but, rather, from pericytes.

Source: New York University

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A Curious Mindset Helps Memory More than an Urgent One

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Photo by Mari Lezhava on Unsplash

New research from Duke University found that shifting to a curious mindset helps memory – such as video game players who imagined being a thief scouting a virtual art museum in preparation for a heist. This mindset resulted in better recalling the paintings there. Adopting a high-pressure mindset, such as players trying to execute the heist, resulted in fewer paintings being recalled.

These subtle differences in motivation – urgent, immediate goal-seeking versus curious exploration for a future goal – have big potential for framing real-world challenges such encouraging vaccination. The findings appeared in PNAS.

Alyssa Sinclair, PhD ’23, a postdoctoral researcher working in the lab of Duke Institute for Brain Sciences director Alison Adcock, PhD, MD, recruited 420 adults to pretend to be art thieves for a day. The participants were then randomly assigned to one of two groups and received different backstories.

“For the urgent group, we told them, ‘You’re a master thief, you’re doing the heist right now. Steal as much as you can!’,” Sinclair said. “Whereas for the curious group, we told them they were a thief who’s scouting the museum to plan a future heist.”

After getting these different backstories, however, participants in the two groups played the exact same computer game, scored the exact same way. They explored an art museum with four coloured doors, representing different rooms, and clicked on a door to reveal a painting from the room and its value. Some rooms held more valuable collections of art. No matter which scenario they were pretending to be in, everyone earned real bonus money by finding more valuable paintings.

The impact of this difference in mindset was most apparent the following day. When participants logged back in, they were met with a pop quiz about whether they could recognise 175 different paintings (100 from the day before, and 75 new ones). If participants flagged a painting as familiar, they also had to recall how much it was worth.

Sinclair and her co-author, fellow Duke psychology & neuroscience graduate student Candice Yuxi Wang, were gratified after they graded the tests to see their predictions had played out.

“The curious group participants who imagined planning a heist had better memory the next day,” Sinclair said. “They correctly recognized more paintings. They remembered how much each painting was worth. And reward boosted memory, so valuable paintings were more likely to be remembered. But we didn’t see that in the urgent group participants who imagined executing the heist.”

Urgent group participants, however, had a different advantage. They were better at figuring out which doors hid more expensive pieces, and as a result snagged more high value paintings. Their stash was appraised at about $230 more than the curious participants’ collection.

The difference in strategies (curious versus urgent) and their outcomes (better memory versus higher-valued paintings) doesn’t mean one is better than the other, though.

“It’s valuable to learn which mode is adaptive in a given moment and use it strategically,” Dr Adcock said.

For example, being in an urgent, high-pressure mode might be the best option for a short-term problem.

“If you’re on a hike and there’s a bear, you don’t want to be thinking about long-term planning,” Sinclair said. “You need to focus on getting out of there right now.”

Opting for an urgent mindset might also be useful in less grisly scenarios that require short-term focus, Sinclair explained, like prompting people to get a COVID vaccine.

For encouraging long-term memory or action, stressing people out is less effective.

“Sometimes you want to motivate people to seek information and remember it in the future, which might have longer term consequences for lifestyle changes,” Sinclair said. “Maybe for that, you need to put them in a curious mode so that they can actually retain that information.”

Sinclair and Wang are now following up on these findings to see how urgency and curiosity activate different parts of the brain. Early evidence suggests that, by engaging the amygdala, an almond-shaped brain region best known for its role in fear memory, “urgent mode” helps form focused, efficient memories. Curious exploration, however, seems to shuttle the learning-enhancing neurochemical dopamine to the hippocampus, a brain region crucial for forming detailed long-term memories.

With these brain results in mind, Dr Adcock is exploring how her lab’s research might also benefit the patients she sees as a psychiatrist.

“Most of adult psychotherapy is about how we encourage flexibility, like with curious mode” Dr Adcock said. “But it’s much harder for people to do since we spend a lot of our adult lives in an urgency mode.”

These thought exercises may give people the ability to manipulate their own neurochemical spigots and develop “psychological manoeuvres,” or cues that act similar to pharmaceuticals, Dr Adcock explained.

“For me, the ultimate goal would be to teach people to do this for themselves,” Dr Adcock said. “That’s empowering.”

Source: Duke University