Those with episodic amnesia are not ‘stuck in time,’ says philosopher Carl Craver

In 1981, a motorcycle accident left Toronto native Kent Cochrane with severe brain damage and dramatically impaired episodic memory. Following the accident, Cochrane could no longer remember events from his past. Nor could he predict specific events that might happen in the future.

When neuroscientist Endel Tulving, PhD, asked him to describe what he would do tomorrow, Cochrane could not answer and described his state of mind as “blank.”

Psychologists and neuroscientists came to know Cochrane, who passed away earlier this year, simply as “KC.” Many scientists have described KC as “stuck in time,” or trapped in a permanent present.

It has generally been assumed that people with episodic amnesia experience time much differently than those with more typical memory function. 

However, a recent paper in Neuropsychologia co-authored by Carl F. Craver, PhD, professor of philosophy and of philosophy-neuroscience-psychology, both in Arts & Sciences at Washington University in St. Louis, disputes this type of claim.

“It’s our whole way of thinking about these people that we wanted to bring under pressure,” Craver said. “There are sets of claims that sound empirical, like ‘These people are stuck in time.’ But if you ask, ‘Have you actually tested what they know about time?’ the answer is no.”

Time and consciousness

A series of experiments convinced Craver and his co-authors that although KC could not remember specific past experiences, he did in fact have an understanding of time and an appreciation of its significance to his life.

Interviews with KC by Craver and his colleagues revealed that KC retained much of what psychologists refer to as “temporal consciousness.” KC could order significant events from his life on a timeline, and he seemed to have complete mastery of central temporal concepts.

For example, KC understood that events in the past have already happened, that they influence the future, and that once they happen, they cannot be changed. 

He also knew that events in the future don’t remain in the future, but eventually become present. Even more interestingly, KC’s understanding of time influenced his decision-making.

If KC truly had no understanding of time, Craver argues, then he and others with his type of amnesia would act as if only the present mattered. Without understanding that present actions have future consequences or rewards, KC would have based his actions only upon immediate outcomes. However, this was not the case.

On a personality test, KC scored as low as possible on measures of hedonism, or the tendency to be a self-indulgent pleasure-seeker.

In systematic tests of his decision-making, carried out with WUSTL’s Len Green, PhD, professor of psychology, and Joel Myerson, PhD, research professor of psychology, and researchers at York University in Toronto, KC also showed that he was willing to trade a smaller, sooner reward for a larger, later reward.

In other words, KC’s inability to remember past events did not affect his ability to appreciate the value of future rewards. 

‘Questions are now wide open’

KC’s case reveals how much is left to discover about memory and how it relates to human understanding of time.

“If you think about memory long enough it starts to sound magical,” Craver said. “How is it that we can replay these events from our lives? And what’s going on in our brains that allows us to re-experience these events from our past?”

Craver hopes that this article — the last to be published about KC during his lifetime — brings these types of questions to the forefront. 

“These findings open up a whole new set of questions about people with amnesia,” Craver said. “Things that we previously thought were closed questions are now wide open.”

(Image credit)

Molecular Switches for Age-Related Memory Decline? A Genetic Variant Protects Against Brain Aging

Even among the healthiest individuals, memory and cognitive abilities decline with age. This aspect of normal aging can affect an individual’s quality of life and capability to live independently but the rate of decline is variable across individuals. There are many factors that can influence this trajectory, but perhaps none more importantly than genetics.

Scientists are seeking to identify key molecular switches that control age-related memory impairment. When new molecules are identified as critical to the process of memory consolidation, they are then tested to determine whether they contribute to the memory problems of the elderly.

One of these proteins is called KIBRA and the gene responsible for its production is WWC1. KIBRA is known to play a role in human memory and so researchers at the Lieber Institute for Brain Development and the National Institute of Mental Health, led by senior author Dr. Venkata Mattay, conducted a study to determine the effects of genetic variants in WWC1 on memory. Their findings are published in the current issue of Biological Psychiatry.

“Identifying these genetic factors, while helping us better understand the neurobiology of cognitive aging, will also aid in identifying mechanisms that confer individuals with resilience to withstand the inevitable age-related changes in neural architecture and function,” explained Mattay.

Using imaging genetics, a method that combines genetics with brain imaging technology, the team explored the effect of a variant in the WWC1 gene on age-related changes in memory function. The particular WWC1 variant under investigation has three potential forms – CC, TT, or CT.

They recruited 233 healthy volunteers, who ranged in age from 18-89 years. The volunteers completed a battery of cognitive tests, underwent genotyping, and completed a memory task during a brain imaging scan.

They found that individuals who carry the T allele, as either CT or TT, performed better on the memory task and showed more active engagement in the hippocampus, a vital brain region for memory, with increasing age.

“Our results show a dynamic relationship between this gene and increasing age on hippocampal function and episodic memory with the non-T allele group showing a significant decline across the adult life span,” said Mattay. “A similar relationship was not observed in the T-allele carrying group suggesting that this variant of the gene may confer a protective effect.”

Dr. John Krystal, Editor of Biological Psychiatry, commented, “The risk mechanisms for age-related memory impairment that we identify today may become the targets for the prevention and treatment of this problem in the future.”

Neuroscientists Find Brain Activity May Mark the Beginning of Memories

By tracking brain activity when an animal stops to look around its environment, neuroscientists at Johns Hopkins University believe they can mark the birth of a memory.

Using lab rats on a circular track, James Knierim, professor of neuroscience in the Zanvyl Krieger Mind/Brain Institute at Johns Hopkins, and a team of brain scientists, noticed that the rats frequently paused to inspect their environment with head movements as they ran. The scientists found that this behavior activated a place cell in their brain, which helps the animal construct a cognitive map, a pattern of activity in the brain that reflects the animal’s internal representation of its environment.

In a paper recently published in the journal Nature Neuroscience, the researchers state that when the rodents passed that same area of the track seconds later, place cells fired again, a neural acknowledgement that the moment has imprinted itself in the brain’s cognitive map in the hippocampus.

The hippocampus is the brain’s warehouse for long- and short-term processing of episodic memories, such as memories of a specific experience like a trip to Maine or a recent dinner. What no one knew was what happens in the hippocampus the moment an experience imprints itself as a memory.

“This is like seeing the brain form memory traces in real time,” said Knierim, senior author of the research. “Seeing for the first time the brain creating a spatial firing field tied to a specific behavioral experience suggests that the map can be updated rapidly and robustly to lay down a memory of that experience.”

A place cell is a type of neuron within the hippocampus that becomes active when an animal or human enters a particular place in its environment. The activation of the cells help create a spatial framework much like a map, that allows humans and animals to know where they are in any given location. Place cells can also act like neural flags that “mark” an experience on the map, like a pin that you drop on Google maps to mark the location of a restaurant.

“We believe that the spatial coordinates of the map are delivered to the hippocampus by one brain pathway, and the information about the things that populate the map, like the restaurant, are delivered by a separate pathway,” said Knierim. “When you experience a new item in the environment, the hippocampus combines these inputs to create a new spatial marker of that experience.”

In the experiments, researchers placed tiny wires in the brains of the rats to monitor when and where brain activity increased as they moved along the track in search of chocolate rewards. About every seven seconds, the rats stopped moving forward and turned their heads to the perimeter of the room as they investigated the different landmarks, a behavior called “head-scanning.”

“We found that many cells that were previously silent would suddenly start firing during a specific head-scanning event,” said Knierim. “On the very next lap around the track, many of these cells had a brand new place field at that exact same location and this place field remained usually for the rest of the laps. We believe that this new place field marks the site of the head scan and allows the brain to form a memory of what it was that the rat experienced during the head scan.”

Knierim said the formation and stability of place fields and the newly-activated place cells requires further study. The research is primarily intended to understand how memories are formed and retrieved under normal circumstances, but it could be applicable to learning more about people with brain trauma or hippocampal damage due to aging or Alzheimer’s.

“There are strong indications that humans and rats share the same spatial mapping functions of the hippocampus, and that these maps are intimately related to how we organize and store our memories of prior life events,” said Knierim. “Since the hippocampus and surrounding brain areas are the first parts of the brain affected in Alzheimer’s, we think that these studies may lend some insight into the severe memory loss that characterizes the early stages of this disease.”

(Image: Shutterstock)

In the brain, timing is everything

Suppose you heard the sound of skidding tires, followed by a car crash. The next time you heard such a skid, you might cringe in fear, expecting a crash to follow — suggesting that somehow, your brain had linked those two memories so that a fairly innocuous sound provokes dread.

MIT neuroscientists have now discovered how two neural circuits in the brain work together to control the formation of such time-linked memories. This is a critical ability that helps the brain to determine when it needs to take action to defend against a potential threat, says Susumu Tonegawa, the Picower Professor of Biology and Neuroscience and senior author of a paper describing the findings in the Jan. 23 issue of Science.

“It’s important for us to be able to associate things that happen with some temporal gap,” says Tonegawa, who is a member of MIT’s Picower Institute for Learning and Memory. “For animals it is very useful to know what events they should associate, and what not to associate.”

The interaction of these two circuits allows the brain to maintain a balance between becoming too easily paralyzed with fear and being too careless, which could result in being caught off guard by a predator or other threat.

The paper’s lead authors are Picower Institute postdocs Takashi Kitamura and Michele Pignatelli.

Linking memories

Memories of events, known as episodic memories, always contain three elements — what, where, and when. Those memories are created in a brain structure called the hippocampus, which must coordinate each of these three elements.

To form episodic memories, the hippocampus also communicates with the region of the cerebral cortex just outside the hippocampus, known as the entorhinal cortex. The entorhinal cortex, which has several layers, receives sensory information, such as sights and sounds, from sensory processing areas of the brain and sends the information on to the hippocampus.

Previous research has revealed a great deal about how the brain links the place and object components of memory. Certain neurons in the hippocampus, known as place cells, are specialized to fire when an animal is in a specific location, and also when the animal is remembering that location. However, when it comes to associating objects and time, “our understanding has fallen behind,” Tonegawa says. “Something is known, but relatively little compared to the object-place mechanism.”

The new Science paper builds on a 2011 study from Tonegawa’s lab in which he identified a brain circuit necessary for mice to link memories of two events — a tone and a mild electric shock — that occur up to 20 seconds apart. This circuit connects layer 3 of the entorhinal cortex to the CA1 region of the hippocampus. When that circuit, known as the monosynaptic circuit, was disrupted, the animals did not learn to fear the tone.

In the new paper, the researchers report the discovery of a previously unknown circuit that suppresses the monosynaptic circuit. This signal originates in a type of excitatory neurons discovered in Tonegawa’s lab, dubbed “island cells” because they form circular clusters within layer 2. Those cells stimulate inhibitory neurons in CA1 that suppress the set of excitatory CA1 neurons that are activated by the monosynaptic circuit.

This circuit creates a counterbalance that limits the window of opportunity for two events to become linked. “This pathway might provide a mechanism for preventing constant learning of unimportant temporal associations,” says Michael Hasselmo, a professor of psychology at Boston University who was not part of the research team.

The findings are “an important demonstration of the functional role of different populations of neurons in entorhinal cortex that provide input to the hippocampus,” Hasselmo adds.

Deciphering circuits

The researchers used optogenetics, a technology that allows specific populations of neurons to be turned on or off with light, to demonstrate the interplay of these two circuits.

In normal mice, the maximum time gap between events that can be linked is about 20 seconds, but the researchers could lengthen that period by either boosting activity of layer 3 cells or suppressing layer 2 island cells. Conversely, they could shorten the window of opportunity by inhibiting layer 3 cells or stimulating input from layer 2 island cells, which both result in turning down CA1 activity.

The researchers hypothesize that prolonged CA1 activity keeps the memory of the tone alive long enough so that it is still present when the shock takes place, allowing the two memories to be linked. They are now investigating whether CA1 neurons remain active throughout the entire gap between events.

Memories Are ‘Geotagged’ With Spatial Information

Using a video game in which people navigate through a virtual town delivering objects to specific locations, a team of neuroscientists from the University of Pennsylvania and Freiburg University has discovered how brain cells that encode spatial information form “geotags” for specific memories and are activated immediately before those memories are recalled.

Their work shows how spatial information is incorporated into memories and why remembering an experience can quickly bring to mind other events that happened in the same place.

"These findings provide the first direct neural evidence for the idea that the human memory system tags memories with information about where and when they were formed and that the act of recall involves the reinstatement of these tags," said Michael Kahana, professor of psychology in Penn’s School of Arts and Sciences.

The study was led by Kahana and professor Andreas Schulze-Bonhage of Freiberg. Jonathan F. Miller, Alec Solway, Max Merkow and Sean M. Polyn, all members of Kahana’s lab, and Markus Neufang, Armin Brandt, Michael Trippel, Irina Mader and Stefan Hefft, all members of Schulze-Bonhage’s lab, contributed to the study. They also collaborated with Drexel University’s Joshua Jacobs.

Their study was published in the journal Science.

Kahana and his colleagues have long conducted research with epilepsy patients who have electrodes implanted in their brains as part of their treatment. The electrodes directly capture electrical activity from throughout the brain while the patients participate in experiments from their hospital beds.

As with earlier spatial memory experiments conducted by Kahana’s group, this study involved playing a simple video game on a bedside computer. The game in this experiment involved making deliveries to stores in a virtual city. The participants were first given a period where they were allowed to freely explore the city and learn the stores’ locations. When the game began, participants were only instructed where their next stop was, without being told what they were delivering. After they reached their destination, the game would reveal the item that had been delivered, and then give the participant their next stop.

After 13 deliveries, the screen went blank and participants were asked to remember and name as many of the items they had delivered in the order they came to mind.

This allowed the researchers to correlate the neural activation associated with the formation of spatial memories (the locations of the stores) and the recall of episodic memories: (the list of items that had been delivered).

“A challenge in studying memory in naturalistic settings is that we cannot create a realistic experience where the experimenter retains control over and can measure every aspect of what the participant does and sees. Virtual reality solves that problem,” Kahana said. “Having these patients play our games allows us to record every action they take in the game and to measure the responses of neurons both during spatial navigation and then later during verbal recall.”

By asking participants to recall the items they delivered instead of the stores they visited, the researchers could test whether their spatial memory systems were being activated even when episodic memories were being accessed. The map-like nature of the neurons associated with spatial memory made this comparison possible.

"During navigation, neurons in the hippocampus and neighboring regions can often represent the patient’s virtual location within the town, kind of like a brain GPS device," Kahana said. "These so-called ‘place cells’ are perhaps the most striking example of a neuron that encodes an abstract cognitive representation."

Using the brain recordings generated while the participants navigated the city, the researchers were able to develop a neural map that corresponded to the city’s layout. As participants passed by a particular store, the researchers correlated their spatial memory of that location with the pattern of place cell activation recorded. To avoid confounding the episodic memories of the items delivered with the spatial memory of a store’s location, the researchers excluded trips that were directly to or from that store when placing it on the neural map.

With maps of place cell activations in hand, the researchers were able to cross- reference each participant’s spatial memories as they accessed their episodic memories of the delivered items. The researchers found that the neurons associated with a particular region of the map activated immediately before a participant named the item that was delivered to a store in that region.

“This means that if we were given just the place cell activations of a participant,” Kahana said, “we could predict, with better than chance accuracy, the item he or she was recalling. And while we cannot distinguish whether these spatial memories are actually helping the participants access their episodic memories or are just coming along for the ride, we’re seeing that this place cell activation plays a role in the memory retrieval processes.”

Earlier neuroscience research in both human and animal cognition had suggested the hippocampus has two distinct roles: the role of cartographer, tracking

location information for spatial memory, and the role of scribe, recording events for episodic memory. This experiment provides further evidence that these roles are intertwined.

“Our finding that spontaneous recall of a memory activates its neural geotag suggests that spatial and episodic memory functions of the hippocampus are intimately related and may reflect a common functional architecture,” Kahana said.

Neuroscientists plant false memories in the brain

The phenomenon of false memory has been well-documented: In many court cases, defendants have been found guilty based on testimony from witnesses and victims who were sure of their recollections, but DNA evidence later overturned the conviction.

In a step toward understanding how these faulty memories arise, MIT neuroscientists have shown that they can plant false memories in the brains of mice. They also found that many of the neurological traces of these memories are identical in nature to those of authentic memories.

“Whether it’s a false or genuine memory, the brain’s neural mechanism underlying the recall of the memory is the same,” says Susumu Tonegawa, the Picower Professor of Biology and Neuroscience and senior author of a paper describing the findings in the July 25 edition of Science.

The study also provides further evidence that memories are stored in networks of neurons that form memory traces for each experience we have — a phenomenon that Tonegawa’s lab first demonstrated last year.

Neuroscientists have long sought the location of these memory traces, also called engrams. In the pair of studies, Tonegawa and colleagues at MIT’s Picower Institute for Learning and Memory showed that they could identify the cells that make up part of an engram for a specific memory and reactivate it using a technology called optogenetics.

Lead authors of the paper are graduate student Steve Ramirez and research scientist Xu Liu. Other authors are technical assistant Pei-Ann Lin, research scientist Junghyup Suh, and postdocs Michele Pignatelli, Roger Redondo and Tomas Ryan.

Seeking the engram

Episodic memories — memories of experiences — are made of associations of several elements, including objects, space and time. These associations are encoded by chemical and physical changes in neurons, as well as by modifications to the connections between the neurons.

Where these engrams reside in the brain has been a longstanding question in neuroscience. “Is the information spread out in various parts of the brain, or is there a particular area of the brain in which this type of memory is stored? This has been a very fundamental question,” Tonegawa says.

In the 1940s, Canadian neurosurgeon Wilder Penfield suggested that episodic memories are located in the brain’s temporal lobe. When Penfield electrically stimulated cells in the temporal lobes of patients who were about to undergo surgery to treat epileptic seizures, the patients reported that specific memories popped into mind. Later studies of the amnesiac patient known as “H.M.” confirmed that the temporal lobe, including the area known as the hippocampus, is critical for forming episodic memories.

However, these studies did not prove that engrams are actually stored in the hippocampus, Tonegawa says. To make that case, scientists needed to show that activating specific groups of hippocampal cells is sufficient to produce and recall memories.

To achieve that, Tonegawa’s lab turned to optogenetics, a new technology that allows cells to be selectively turned on or off using light.

For this pair of studies, the researchers engineered mouse hippocampal cells to express the gene for channelrhodopsin, a protein that activates neurons when stimulated by light. They also modified the gene so that channelrhodopsin would be produced whenever the c-fos gene, necessary for memory formation, was turned on.

In last year’s study, the researchers conditioned these mice to fear a particular chamber by delivering a mild electric shock. As this memory was formed, the c-fos gene was turned on, along with the engineered channelrhodopsin gene. This way, cells encoding the memory trace were “labeled” with light-sensitive proteins.

The next day, when the mice were put in a different chamber they had never seen before, they behaved normally. However, when the researchers delivered a pulse of light to the hippocampus, stimulating the memory cells labeled with channelrhodopsin, the mice froze in fear as the previous day’s memory was reactivated.

“Compared to most studies that treat the brain as a black box while trying to access it from the outside in, this is like we are trying to study the brain from the inside out,” Liu says. “The technology we developed for this study allows us to fine-dissect and even potentially tinker with the memory process by directly controlling the brain cells.”

Incepting false memories

That is exactly what the researchers did in the new study — exploring whether they could use these reactivated engrams to plant false memories in the mice’s brains.

First, the researchers placed the mice in a novel chamber, A, but did not deliver any shocks. As the mice explored this chamber, their memory cells were labeled with channelrhodopsin. The next day, the mice were placed in a second, very different chamber, B. After a while, the mice were given a mild foot shock. At the same instant, the researchers used light to activate the cells encoding the memory of chamber A.

On the third day, the mice were placed back into chamber A, where they now froze in fear, even though they had never been shocked there. A false memory had been incepted: The mice feared the memory of chamber A because when the shock was given in chamber B, they were reliving the memory of being in chamber A.

Moreover, that false memory appeared to compete with a genuine memory of chamber B, the researchers found. These mice also froze when placed in chamber B, but not as much as mice that had received a shock in chamber B without having the chamber A memory activated.

The researchers then showed that immediately after recall of the false memory, levels of neural activity were also elevated in the amygdala, a fear center in the brain that receives memory information from the hippocampus, just as they are when the mice recall a genuine memory.

These two papers represent a major step forward in memory research, says Howard Eichenbaum, a professor of psychology and director of Boston University’s Center for Memory and Brain.

“They identified a neural network associated with experience in an environment, attached a fear association with it, then reactivated the network to show that it supports memory expression. That, to me, shows for the first time a true functional engram,” says Eichenbaum, who was not part of the research team.

The MIT team is now planning further studies of how memories can be distorted in the brain.

“Now that we can reactivate and change the contents of memories in the brain, we can begin asking questions that were once the realm of philosophy,” Ramirez says. “Are there multiple conditions that lead to the formation of false memories? Can false memories for both pleasurable and aversive events be artificially created? What about false memories for more than just contexts — false memories for objects, food or other mice? These are the once seemingly sci-fi questions that can now be experimentally tackled in the lab.”

Never forget a face? Researchers find women have better memory recall than men

New research from McMaster University suggests women can remember faces better than men, in part because they spend more time studying features without even knowing it, and a technique researchers say can help improve anyone’s memories.

The findings help to answer long-standing questions about why some people can remember faces easily while others quickly forget someone they’ve just met.

“The way we move our eyes across a new individual’s face affects our ability to recognize that individual later,” explains Jennifer Heisz, a research fellow at the Rotman Research Institute at Baycrest Health Sciences and newly appointed assistant professor in the Department of Kinesiology at McMaster University.

She co-authored the paper with David Shore, psychology professor at McMaster and psychology graduate student Molly Pottruff.

“Our findings provide new insights into the potential mechanisms of episodic memory and the differences between the sexes. We discovered that women look more at new faces than men do, which allows them to create a richer and more superior memory,” Heisz says.

Eye tracking technology was used to monitor where study participants looked—be it eyes, nose or mouth—while they were shown a series of randomly selected faces on a computer screen. Each face was assigned a name that participants were asked to remember.

One group was tested over the course of one day, another group tested over the course of four days.

“We found that women fixated on the features far more than men, but this strategy operates completely outside of our awareness. Individuals don’t usually notice where their eyes fixate, so it’s all subconscious.”

The implications are exciting, she says, because it means anyone can be taught to scan more and potentially have better memory.

“The results open the possibility that changing our eye movement pattern may lead to better memory,” says Shore. “Increased scanning may prove to be a simple strategy to improve face memory in the general population, especially for individuals with memory impairment like older adults.”

Clenching Right Fist May Give Better Grip On Memory

Clenching your right hand may help form a stronger memory of an event or action, and clenching your left may help you recollect the memory later, according to research published April 24 in the open access journal PLOS ONE by Ruth Propper and colleagues from Montclair State University.

Participants in the research study were split into groups and asked to first memorize, and later recall words from a list of 72 words. There were 4 groups who clenched their hands; One group clenched their right fist for about 90 seconds immediately prior to memorizing the list and then did the same immediately prior to recollecting the words. Another group clenched their left hand prior to both memorizing and recollecting. Two other groups clenched one hand prior to memorizing (either the left or right hand) and the opposite hand prior to recollecting. A control group did not clench their fists at any point.

The group that clenched their right fist when memorizing the list and then clenched the left when recollecting the words performed better than all the other hand clenching groups. This group also did better than the group that did not clench their fists at all, though this difference was not statistically ‘significant’.

"The findings suggest that some simple body movements — by temporarily changing the way the brain functions- can improve memory. Future research will examine whether hand clenching can also improve other forms of cognition, for example verbal or spatial abilities," says Ruth Propper, lead scientist on the study.

The authors clarify that further work is needed to test whether their results with word lists also extend to memories of visual stimuli like remembering a face, or spatial tasks, such as remembering where keys were placed. Based on previous work, the authors suggest that this effect of hand-clenching on memory may be because clenching a fist activates specific brain regions that are also associated with memory formation.

Reconstructing the Past: How Recalling Memories Alters Them

Recently the neurologist and author Oliver Sacks recalled a vivid childhood memory, recounted in his autobiography, Uncle Tungsten.

During WWII he lived in London during the Blitz, and on one occasion:

"…an incendiary bomb, a thermite bomb, fell behind our house and burned with a terrible, white-hot heat. My father had a stirrup pump, and my brothers carried pails of water to him, but water seemed useless against this infernal fire—indeed, made it burn even more furiously. There was a vicious hissing and sputtering when the water hit the white-hot metal, and meanwhile the bomb was melting its own casing and throwing blobs and jets of molten metal in all directions."

Except when his autobiography came out, one of his older brothers told him he’d misremembered the event. In fact both of them had been at school when the bomb struck so they could not have witnessed the explosion.

The ‘false’ memory, it turned out, was implanted by a letter. Their elder brother had written to them, describing the frightening event, and this had lodged in his mind. Over the years the letter had gone from a third-person report to a first-person ‘memory’.

Turning the memory over in his mind, Sacks writes that he still cannot see how the memory of the bomb exploding can be false. There is no difference between this memory and others he knows to be true; it felt like he was really there.

This sort of experience is probably much more common than we might like to imagine. Many memories which have the scent of authenticity may turn out to be misremembered, if not totally fictitious events, if only we could check. Without some other source with which to corroborate, it is hard verify the facts, especially for events that took place long ago.

That these sorts of distortions to memory happen is unquestioned, what fascinates is how it comes about. Does the long passage of time warp the memory, or is there some more active process that causes the change?

A study published recently sheds some light on this process and provides a model for how memories like Sack’s become distorted.

Researchers develop tool for reading the minds of mice

If you want to read a mouse’s mind, it takes some fluorescent protein and a tiny microscope implanted in the rodent’s head.

Stanford scientists have demonstrated a technique for observing hundreds of neurons firing in the brain of a live mouse, in real time, and have linked that activity to long-term information storage. The unprecedented work could provide a useful tool for studying new therapies for neurodegenerative diseases such as Alzheimer’s.

The researchers first used a gene therapy approach to cause the mouse’s neurons to express a green fluorescent protein that was engineered to be sensitive to the presence of calcium ions. When a neuron fires, the cell naturally floods with calcium ions. Calcium stimulates the protein, causing the entire cell to fluoresce bright green.

A tiny microscope implanted just above the mouse’s hippocampus – a part of the brain that is critical for spatial and episodic memory – captures the light of roughly 700 neurons. The microscope is connected to a camera chip, which sends a digital version of the image to a computer screen.

The computer then displays near real-time video of the mouse’s brain activity as a mouse runs around a small enclosure, which the researchers call an arena.

The neuronal firings look like tiny green fireworks, randomly bursting against a black background, but the scientists have deciphered clear patterns in the chaos.

"We can literally figure out where the mouse is in the arena by looking at these lights," said Mark Schnitzer, an associate professor of biology and of applied physics and the senior author on the paper, recently published in the journal Nature Neuroscience.

When a mouse is scratching at the wall in a certain area of the arena, a specific neuron will fire and flash green. When the mouse scampers to a different area, the light from the first neuron fades and a new cell sparks up.

"The hippocampus is very sensitive to where the animal is in its environment, and different cells respond to different parts of the arena," Schnitzer said. "Imagine walking around your office. Some of the neurons in your hippocampus light up when you’re near your desk, and others fire when you’re near your chair. This is how your brain makes a representative map of a space."

The group has found that a mouse’s neurons fire in the same patterns even when a month has passed between experiments. “The ability to come back and observe the same cells is very important for studying progressive brain diseases,” Schnitzer said.