The "world's first" mind-reading chip

CHINESE  have developed the "world's first" mind-reading chip that they claim enables people to control computers using just brain signals. Brain-computer interfaces (BCIs) are devices that have been designed to create simple communication between the human brain and computers.

A collaboration between Tianjin University and the state-owned China Electronics Corporation led to the recent unveiling of “Brain Talker,” a computer chip designed specifically for use in BCIs.

“The signals transmitted and processed by the brain are submerged in the background noise,” Tianjin University researcher Ming Dong said in a press release. “This BC3 [Brain-Computer Codec Chip] has the ability to discriminate minor neural electrical signals and decode their information efficiently, which can greatly enhance the speed and accuracy of brain-computer interfaces.”

Ming believes the chip could help bring BCIs out of labs and into the mainstream.
 "The Brain Talker chip advances BCI technology allowing it to become more portable, wearable, and accessible to the general public."

In future, this technology could be used for a variety of purposes, such as imparting education to disabled people, gaming, or creating medical devices for people that have problems with body movements, for example, those suffering from motor neurone disease.
The researchers have not yet revealed whether Brain Talker will be worn outside the body or embedded in the user's brain.

https://futurism.com/the-byte/brain-computer-interfaces-brain-talker
https://www.thesun.co.uk/tech/9221469/china-invents-mind-reading-brain-chip/
https://www.theinquirer.net/inquirer/news/3076931/chinese-boffins-create-brain-talker-chip-that-can-read-your-mind

How estradiol/progesterone participate in cognitive function in women

Thanks ;Castalia Francon
An Interesting Study Reveals how the Hippocampus/Cortex Work Together

Sex Differences? Of Course
Women use spatial navigation just before their periods, but rely more on cues from their surroundings during ovulation.

The present study shows that menstrual cycle phase influences the type of memory system that is likely to be engaged in by women when solving a task or effectively navigating a virtual environment. However, the finding of this study which deserves more focus is that Progesterone, as it varies over the monthly cycle, is found to be a key modulator of which strategy is utilized. in fact as the researchers state, their initial hypotheses, which did not take Progesterone levels sufficiently into account as being a key determinant, were proved wrong.
Different learning systems were first documented by Tolman and colleagues (1946) who showed that rats utilize different strategies to find their way in a maze . Namely, several learning strategies can be used: one is response strategy, which is a strategy that relies on body turns at specific points in the environment forming stimulus- response associations, and the second is spatial strategy, which is allocentric, i.e. independent of the position of the observer and relies on forming stimulus–stimulus associations between land- marks in order to create a cognitive map of the environment.
These systems are dissociable, they can be competitive, and rely on dif- ferent brain regions to function optimally. The hippocampus is implicated in spatial memory whereas the dorsal striatum (which includes the caudate nucleus) is crucial for response memory
Women tested in the mid/late luteal phase, when P is high, use a spatial strategy significantly more than a response strategy. In contrast, during the early follicular (low E2 and P) and ovulatory (high E2) phases, response strategy was used more fre- quently
Thus, these results do NOT support our hypothesis that a high E2 state would be associated with spa tial strategy use and a low E2 state with higher proportion of response strategy use, BUT they suggest that multiple memory system bias in cycling women is mediated by changes in P such that response memory is promoted when P is low, and spatial memory is enhanced in the phase of the cycle that is characterized by high P levels.
The mid/late luteal phase, when P is high, is associated with a significant increase of spatial strategy. Conversely, a response strategy is used in the early follicular and ovulatory phase, when P is low. Thus, it would appear that multiple memory system bias is mediated by changes in P and, possibly, how P and E2 interact.
Consistent with other studies (Maki et al., 2002; Mordecai et al., 2008; ), here, women learned and remembered more words during the ovulatory phase, when E2 levels are high.
These findings support the growing body of research showing that cognitive func- tion is modulated by and change with fluctuating hormones across the menstrual cycle.
It has been consistently shown in rodents that estrogen impacts multiple memory system bias such that low estradiol (E2) is associated with increased use of a striatal-mediated response strategy whereas high E2 increases use of a hippocampal-dependent spatial memory.
It has been observed that E2 is associ- ated with changes in cognition in women; for example, E2 has been linked with improved verbal memory whereas it is associated with impaired performance on mental rotation tasks Hippocampal volume changes across the menstrual cycle in women, i.e., high endogenous E2 levels are asso- ciated with an increase in hippocampal grey matter
In addition, it has previously been found that estrogen receptors are present in the human hippocampus . Thus, E2 could be structurally altering the hippocampus and binding to estrogen receptors within this brain area to promote spatial memory.
Progesterone (P) has been shown to be associated with both enhanced and disrupting (Freeman et al., 1992) effects on verbal memory in women. It is important to note that the majority of studies that are focused on hormones and cognition in women, are carried out with a post- menopausal sample, taking hormone replacements.
These samples of women typically receive progestin with their hormone treat- ments that include E2, thus, very few studies have focused on the effects of P in isolation. P has been shown to increase hippocampal spine density when administered with E2, but these spine den- sities decrease more rapidly than when E2 is administered alone
P receptor function is dependent on induction of E2 receptors (Lydon et al., 1995), which suggests that many of the effects linked to P are also underscored by E2 action. Furthermore, E2 and P are often studied separately so the interac- tion between the two hormones, and how this can potentially affect cognitive function, is not well understood. E2 and P seem to work in concert to affect hippocampal function and, possibly, multiple memory system bias.
Participants were split into either an early follicular (i.e., when E2 levels are low), ovulatory (i.e., when E2 levels are high) or mid/late luteal (i.e., end of the cycle, when E2 levels decrease and progesterone levels rise) phase group, using self-reported date of the menstrual cycle. Serum hormone level measurements (E2, progesterone, testosterone) were used to confirm cycle phase assignment.
NOTE: Recall that Estradiol peaks towards the end of the follicular phase (ovulation) and then rises and plateaus across the luteal phase. The menstrual cycle is also marked by changes in P levels such that they are low throughout the follic- ular phase while they peak and plateau in the luteal phase, before dropping at the onset of menstruation (for review, see Ref.: Hussain et al., 2014; Mihm et al., 2011). E2 levels are higher in the ovulatory phase compared to the early follicular phase, which is marked by low E2 levels throughout menstruation
We used a virtual navigation task. Basically, it was like a video game where women had to find their way through a maze. The maze can be completed either by using the cues in one’s surroundings and making a mental (cognitive) map of the area, or by remembering where each maze arm is relative to another, for example noting that you have to skip two arms then take the next arm. Later we remove the surrounding cues and see how well or poorly someone completing the maze does. This allows us to test which memory system they preferentially use.
Participants were administered a verbal memory task as well as a virtual navigation task that can be solved by using either a response or spatial strategy. Women tested in the ovulatory phase, under high E2 conditions, performed better on a verbal memory task than women tested during the other phases of the cycle
We found that during the ovulatory phase when estrogen peaks, women tend to use response memory to solve the maze. Asked to navigate a virtual maze, most women who are ovulating (i.e., when E2 levels are high) will rely on response memory, using cues from their surroundings to memorize turns.
Response memory is like basic habitual motor memory, such as turning right then left to get to work. However, when women are in the mid/late luteal phase of the cycle, just prior to menstruation when progesterone peaks and estrogen also rises again, they are more likely to use spatial memory.
Women in the premenstrual phase of their cycle, however, relied on spatial memory, picturing an aerial map of the maze in their heads.
Interestingly, women tested in the mid/late luteal phase mid/late luteal (i.e., end of the cycle, when E2 levels decrease and progesterone levels rise) when progesterone is high, predominantly used a spatial strategy, whereas the opposite pattern was observed in the early follicular and ovulatory groups
Spatial memory is what you’d use if you encountered a roadblock on your way to work, and had to mentally pull up a map of the neighborhood to think of an alternate rout
An interesting set of observations here, but we suspect that they might be more strongly phrased in terms of the details and mechanisms of hippocampal/cortical partnering in regard to the two different situations. In other words it is our belief that it would indicate more to state that the landmarks..and so called "response" strategy were dependent on cued recall by the women and thus reliant on the arisal of verbal or other indices via a process akin to "episodic memory recall". This would go hand in hand with the performance on the verbal recall test, as well.
What is more problematic to us is that the researchers do not have a suficiently articulated or sophisticated view of just how it is that the hippocampus works in tandem with other systems to aid in both navigation and in episodic memory.
The 'response" strategy is not sufficiently appreciated as depending upon much more than some merely "procedural" movement control function. The "responses" in that strategy depend on a back and forth dialogue with 'episodically" based neuronal ensembles in the hippocampal area that are accessible via verbal and cortical efforts....and to which priority is given by the user. On the contrary the spatial strategy is one where the user has faith in the mapping and the abstract spatial configurations implied by the geometry of the "map" being relied upon.
It is truly frequently disheartening to watch neuroscience researchers seemingly lost in a maze of their own when trying to speak coherently and usefully about how the hippocampus works. The segmentation of hippocampal function into some truly insipid aspect such as "verbal memory" that is apart and not ever articulated in terms of how it related to the other more well known functioning of the hippocampus in spatial navigation is truly an egregious omission...and the researchers deserve to be befuddled by their own data.
Clearly both these aspects of the hippocampus, verbal recall and navigation, MUST have something to do with each other. Yet they are treated as if they are too randomly placed items on a supermarket shelf to be selected by the researcher shopping for a research project. g
The verbal recall testing was enhanced during high Estradiol times of month...so you would think that the question of the potential inverse relation between performance on the two types of tests would be even briefly considered by the researchers. But alas they don't get very far at all. In fact they flounder in their discussion through a variety of statisfical and other more superficial factors as causing their unexpected results, rather than focus on better DEFINING just how it might be that the hippocampus does its job..or jobs.
One of the points they do raise, to their credit, but only in passing is that It has been shown that hormonal changes across the cycle are also related with changes in lateraliza- tion during completion of a verbal task, such that lateralization is pronounced when E2 levels are low.
This should reasonably raise the notion that the hippocampus, too, has a left and right part, and that episodic memory as measured by verbal recall (as badly as that is defined) tends to depend on the left hippocampal areas and that the female hormone mix might indeed tend to lead to less "lateralization" within the hippocampus as well...and thus recruit both of its aspects in task performance? Sounds reasonable to us..but this is not discussed.
Additionally of the problem here is the surprise that Progesterone plays a vital function in modulating how Estradiol impacts upon the brain and the manner in which women choose to cope with events. The precedent studies were frequently based on work with rats and humans may be different from rodents in this regard. Here, both the lowest and highest E2 levels observed across the cycle were associated with response strategy use. The difference observed in how E2 impacts multiple memory system bias in rodents and in humans could be explained by the significant difference between the rat estrous cycle and the human menstrual cycle. In rats, E2 and P peak concurrently, such that a high E2 phase is also marked by high P.
Conversely, in women, the two hormones fluctuate dif- ferently and peak at different points in the cycle. It is possible that ovarian hormones interact differently in the human brain and, thus, affect cognitive functions, such as multiple memory system bias, in a unique way.
This interaction is critical in unraveling the mysteries of hormonal effect on preference of cognitive strategy and effectiveness of use, however, the absolutely incomopetent and bogus Women's Health Initiative studies of the early 2000;s along with the almost fraudulent coverup by the medical cronies of those who incompegtently conducted those studies created massive confusion not only among clinicians but among researchers as the difference betwen use of 'Progesterone" (the real thing) and various Toxic syntheic "progestagens" (formulated by big Pharma who sponsored the studies and has continued to promote the use of these toxic medications.
These "progestagens" do NOT act upon the brain and its neurosteroids and its neurotransmitters in the same way as bio identical Progesterone does..and in fact has some directly antithetical effects.
So as we read the literature search and discussions of current articles we find them totally confused, misinformed and practically incoherent in trying to reason out why they have such conflicting results on Estradiol and "progestagen" use'.. Thus, the WHI not only led to the damaging of the health of countless women but also succeeding in sabotaging the research data on the basis of which researchers such as the ones here have predicated their own research designs.
A Few comments from the Authors when Interviewed
https://www.researchgate.net/…/how-women-navigate-depends-o…
RG: What is the significance of these results?
Brake: While we have known for years that estrogen affects the brain to cause memory bias in female rodents, this is the first study to see how hormones affect women's memory.
RG: Does birth control interfere with these preferences for one memory strategy over another?
Brake: We did not test women on birth control, but I would imagine that it could affect memory bias, depending on the form and dose.
Would you recommend changes to the way studies involving memory tasks are conducted in light of your results?
I would certainly note that researchers studying memory in women or female mammals should control for hormone levels.
RG: What led you to look into the effects of hormones on memory bias?
Brake: It's about bloody time that we start understanding more about the female brain. Every mental disorder or disease, every single one, has a sex bias.
Yet, we still mostly only study the brains of men. Since researchers began studying the brain, they’ve known that studying the female brain is messy. There was more variability, which people suspect could be accounted for by changes in circulating ovarian hormones, so many people couldn't be bothered with all that extra variability in their studies.
DOI: 10.1016/j.psyneuen.2016.05.008
Aside from the likelihood of significantly misleading data that undoubtedly has been arising from various navigation studies and attempts to understand hippocampal function, we note the related issues of lesser importance but one with which we can identify: Getting around via Digital Maps and Navigational Aids:
Why Your Maps Should Get in Touch with Their Feminine Side
http://www.xyht.com/spatial-i…/maps-get-touch-feminine-side/

The Way the Brain Creates a Timeline of the Past

Cecile G. Tamura
The brain can’t directly encode the passage of time, but recent work hints at a workaround for putting timestamps on memories of events.
https://bit.ly/2N6PDc0

"As sensory neurons fire in response to an unfolding event, the brain maps the temporal component of that activity to some intermediate representation of the experience — a Laplace transform, in mathematical terms.
That representation allows the brain to preserve information about the event as a function of some variable it can encode rather than as a function of time (which it can’t). The brain can then map the intermediate representation back into other activity for a temporal experience — an inverse Laplace transform — to reconstruct a compressed record of what happened when." https://bit.ly/1vfaaPE
Other scientists independently uncovered neurons, dubbed “time cells,” that were “as close as we can possibly get to having that explicit record of the past. These cells were each tuned to certain points in a span of time, with some firing, say, one second after a stimulus and others after five seconds, essentially bridging time gaps between experiences. Scientists could look at the cells’ activity and determine when a stimulus had been presented, based on which cells had fired. This was the inverse-Laplace-transform part of the researchers’ framework, the approximation of the function of past time. “
“A second can last forever. Days can vanish. It’s this coding by parsing episodes that, to me, makes a very neat explanation for the way we see time. We’re processing things that happen in sequences, and what happens in those sequences can determine the subjective estimate for how much time passes.”
That timeline could be of use not just to episodic memory in the hippocampus, but to working memory in the prefrontal cortex and conditioning responses in the striatum.
Scientists also started to show that the same equations that the brain could use to represent time could also be applied to space, numerosity (our sense of numbers) and decision-making based on collected evidence — really, to any variable that can be put into the language of these equations. “For me, what’s appealing is that you’ve sort of built a neural currency for thinking, If you can write out the state of the brain … what tens of millions of neurons are doing … as equations and transformations of equations, that’s thinking."
One day cognitive models could even lead to a new kind of artificial intelligence built on a different mathematical foundation than that of today’s deep learning methods. Only last month, scientists built a novel neural network model of time perception, which was based solely on measuring and reacting to changes in a visual scene.
But before any application to AI is possible, scientists need to ascertain how the brain itself is achieving this.

Graphene can hear your brain whisper

The body of knowledge about the human brain is keeps growing, but many questions remain unanswered. Researchers have been using electrode arrays to record the brain's electrical activity for decades, mapping activity in different brain regions to understand what it looks like when everything is working, and what is happening when it is not. Until now, however, these arrays have only been able to detect activity over a certain frequency threshold. A new technology developed by the Graphene Flagship overcomes this technical limitation, unlocking the wealth of information found below 0.1 Hz, while paving the way for future brain-computer interfaces.

The new device was developed thanks to a collaboration between three Graphene Flagship Partners (IMB-CNM, ICN2 and ICFO) and adapted for brain recordings together with biomedical experts at IDIBAPS. This new technology moves away from electrodes and uses an innovative transistor-based architecture that amplifies the brain's signals in situ before transmitting them to a receiver. The use of graphene to build this new architecture means the resulting implant can support many more recording sites than a standard electrode array. It is slim and flexible enough to be used over large areas of the cortex without being rejected or interfering with normal brain function. The result is an unprecedented mapping of the low frequency brain activity known to carry crucial information about different events, such as the onset and progression of epileptic seizures and strokes.
For neurologists this means they finally have access to some clues that our brains only whisper. This ground-breaking technology could change the way we record and view electrical activity from the brain. Future applications will give unprecedented insights into where and how seizures begin and end, enabling new approaches to the diagnosis and treatment of epilepsy.

"Beyond epilepsy, this precise mapping and interaction with the brain has other exciting applications," explains José Antonio Garrido, one of the leaders of the study working at Graphene Flagship Partner ICN2. "In contrast to the common standard passive electrodes, our active graphene-based transistor technology will boost the implementation of novel multiplexing strategies that can increase dramatically the number of recording sites in the brain, leading the development of a new generation of brain-computer interfaces." Taking advantage of 'multiplexing', this graphene-enabled technology can also be adapted by some of the same researchers to restore speech and communication. ICN2 has secured this technology through a patent that protects the use of graphene-based transistors to measure low-frequency neural signals.


"This work is a prime example of how a flexible, graphene-based transistor array technology can offer capabilities beyond what is achievable today, and open up tremendous possibilities for reading at unexplored frequencies of neurological activity" noted by Kostas Kostarelos, leader of the Health, Medicine and Sensors Division of the Graphene Flagship.

Andrea C. Ferrari, Science and Technology Officer of the Graphene Flagship, and Chair of its Management Panel added that "graphene and related materials have major opportunities for biomedical applications. The Graphene Flagship recognized this by funding a dedicated Work Package. The results of this study are a clear demonstration that graphene can bring unprecedented progress to the study of Brain processes."
This new technology will be one of the Graphene Pavilion's main attractions at the upcoming Mobile World Congress in Barcelona (25-28 February 2019). The exhibition will showcase the latest innovations on graphene and related materials made possible by the Graphene Flagship, one of the biggest research initiatives ever funded by the European Commission. Beyond applications in health and medical devices, the pavilion will be populated with new prototypes of graphene-enabled technologies for mobile and data communications, wearables, and the internet of things.

High-resolution mapping of infraslow cortical brain activity enabled by graphene microtransistors
Eduard Masvidal-Codina, Xavi Illa, Miguel Dasilva, Andrea Bonaccini Calia, Tanja Dragojević, Ernesto E. Vidal-Rosas, Elisabet Prats-Alfonso, Javier Martínez-Aguilar, Jose M. De la Cruz, Ramon Garcia-Cortadella, Philippe Godignon, Gemma Rius, Alessandra Camassa, Elena Del Corro, Jessica Bousquet, Clement Hébert, Turgut Durduran, Rosa Villa, Maria V. Sanchez-Vives, Jose A. Garrido & Anton Guimerà-Brunet
https://www.nanotechnologyworld.org/…/Graphene-can-hear-you…

Scientists Discover Atomic-resolution Details of Brain Signaling

Scientists have revealed never-before-seen details of how our brain sends rapid-fire messages between its cells. They mapped the 3-D atomic structure of a two-part protein complex that controls the release of signaling chemicals, called neurotransmitters, from brain cells.
Understanding how cells release those signals in less than one-thousandth of a second could help launch a new wave of research on drugs for treating brain disorders.

 
The experiments, at the Linac Coherent Light Source (LCLS) X-ray laser at the Department of Energy’s SLAC National Accelerator Laboratory, build upon decades of previous research at Stanford University, Stanford School of Medicine and SLAC. Researchers reported their latest findings today in the journal Nature.

“This is a very important, exciting advance that may open up possibilities for targeting new drugs to control neurotransmitter release. Many mental disorders, including depression, schizophrenia and anxiety, affect neurotransmitter systems,” said Axel Brunger, the study’s principal investigator. He is a professor at Stanford School of Medicine and SLAC and a Howard Hughes Medical Institute investigator.

“Both parts of this protein complex are essential,” Brunger said, “but until now it was unclear how its two pieces fit and work together.”
Unraveling the Combined Secrets of Two Proteins

The two protein parts are known as neuronal SNAREs and synaptotagmin-1.

Earlier X-ray studies, including experiments at SLAC’s Stanford Synchrotron Radiation Lightsource (SSRL) nearly two decades ago, shed light on the structure of the SNARE complex, a helical protein bundle found in yeasts and mammals. SNAREs play a key role in the brain’s chemical signaling by joining, or “fusing,” little packets of neurotransmitters to the outer edges of neurons, where they are released and then dock with chemical receptors in another neuron to trigger a response.

A ‘Smoking Gun’ for Neurotransmitter Release

In this latest research, the scientists found that when the SNAREs and synaptotagmin-1 join up, they act as an amplifier for a slight increase in calcium concentration, triggering a gunshot-like release of neurotransmitters from one neuron to another. They also learned that the proteins join together before they arrive at a neuron’s membrane, which helps to explain how they trigger brain signaling so rapidly.

“The neuron is not building the ‘gun’ as it sits there on the membrane – it’s already there,” Brunger said.

The team speculates that several of the joined protein complexes may group together and simultaneously interact with the same vesicle to efficiently trigger neurotransmitter release, an exciting area for further studies.

“The structure of the SNARE-synaptotagmin-1 complex is a milestone that the field has awaited for a long time, and it sets the framework for a better understanding of the system,” said James Rothman, a professor at Yale University who discovered the SNARE proteins and shared the 2013 Nobel Prize in Physiology or Medicine.

Thomas C. Südhof, a professor at the Stanford School of Medicine and Howard Hughes Medical Institute investigator who shared that 2013 Nobel Prize with Rothman, discovered synaptotagmin-1 and showed that it plays an important role as a calcium sensor and calcium-dependent trigger for neurotransmitter release.

“The new structure has identified unanticipated interfaces between synaptotagmin-1 and the neuronal SNARE complex that change how we think about their interaction by revealing, in atomic detail, exactly where they bind together,” Südhof said. “This is a new concept that goes much beyond previous general models of how synaptotagmin-1 functions.”

Using Crystals, Robotics and X-rays to Advance Neuroscience

To study the joined protein structure, researchers in Brunger’s laboratory at the Stanford School of Medicine found a way to grow crystals of the complex. They used a robotic system developed at SSRL to study the crystals at SLAC’s LCLS, an X-ray laser that is one of the brightest sources of X-rays on the planet. SSRL and LCLS are DOE Office of Science User Facilities.

The researchers combined and analyzed hundreds of X-ray images from about 150 protein crystals to reveal the atomic-scale details of the joined structure.

SSRL’s Aina Cohen, who oversaw the development of the highly automated platform used for the neuroscience experiment, said, “This experiment was the first to use this robotic platform at LCLS to determine a previously unsolved structure of a large, challenging multi-protein complex.” The study was also supported by X-ray experiments at SSRL and at Argonne National Laboratory’s Advanced Photon Source.

“This is a good example of how advanced tools, instruments and X-ray methods are providing us new insights into what are truly complex mechanisms,” Cohen said.

Brunger said future studies will explore other protein interactions relevant to neurotransmitter release. “What we studied is only a subset,” he said. “There are many other factors interacting with this system and we want to know what these look like. This by no means is the end of the story.”

In addition to researchers at SLAC, Stanford University and the Stanford School of Medicine, other contributing scientists were from Lawrence Berkeley National Laboratory. The research was supported by the Howard Hughes Medical Institute; the National Institutes of Health (NIH); the DOE Office of Science; and the SSRL Structural Molecular Biology Program, which is also supported by the DOE Office of Science and the NIH’s National Institute of General Medical Sciences.
https://www.nanotechnologyworld.org/…/Scientists-Discover-A…

The downstairs brain and the upstairs brain

Picture a brain like a house. Downstairs is where important things live. Basic functions like breathing, strong emotions, and innate reactions to danger, like fight, flight or freeze. It’s like the downstairs of a house, which is where we almost always find the basics—kitchen, living room, bathroom.
 The upstairs brain is more complex. Thinking, imagining, planning – these things come from the upstairs brain. We use the upstairs brain to think critically, problem solve, and make good decisions. Important to note for those of us working with teens, the upstairs brain is not fully formed until our mid-20s!
When born the downstairs brain is fully formed, this is where all big emotions come from: fear, anxiety, melt downs, fight flight, freeze.

The upstairs brain is different, this is underdeveloped and this is where parents can help. The upstairs brain deals with problem solving, decision making, calming down.
This link is fantastic to help parents and children understand emotional development and why children " flip their lids" .

Males remember previous pain clearly than females

Scientists increasingly believe that one of the driving forces in chronic pain--the number one health problem in both prevalence and burden--appears to be the memory of earlier pain. Research published in Current Biology suggests that there may be variations, based on sex, in the way that pain is remembered in both mice and humans.

The research team found that men (and male mice) remembered earlier painful experiences clearly. As a result, they were stressed and hypersensitive to later pain when returned to the location in which it had earlier been experienced. Women (and female mice) did not seem to be stressed by their earlier experiences of pain. The researchers believe that the robust translational nature of the results, from mice to men, will potentially aid scientists to move forward in their search for future treatments of chronic pain.

Creating memories of pain in humans and mice

In experiments with both humans and mice, the subjects (41 men and 38 women between the ages of 18-40 in the case of humans) were taken to a specific room (or put in a testing container of a certain shape—depending on the species) where they experienced low levels of pain caused by heat delivered to their hind paw or forearm. Humans rated the level of pain on a 100-point scale and mice “rated” the pain by how quickly they moved away from the heat source. Immediately following this initial experience of low-level pain, subjects experienced more intense pain designed to act as Pavlovian conditioning stimuli. The human subjects were asked to wear a tightly inflated blood pressure cuff and exercise their arms for 20 minutes. This is excruciating and only seven of the 80 subjects rated it at less than 50 on a 100-point scale. Each mouse received a diluted injection of vinegar designed to cause a stomach ache for about 30 minutes.

In order to look at the role that memory plays in the experience of pain, the following day the subjects returned to either the same or a different room, or to the same or a different testing container. Heat was once again applied to their arms or hind paws.

When (and only when) they were taken into the same room as in the previous test, the men rated the heat pain higher than they did the day before, and higher than the women did. Similarly, male, but not female mice returning to the same environment exhibited a heightened heat pain response, while mice placed in a new and neutral environment did not.

“We believe that the mice and the men were anticipating the cuff, or the vinegar, and, for the males, the stress of that anticipation caused greater pain sensitivity,” says Mogil. “There was some reason to expect that we would see increased sensitivity to pain on the second day, but there was no reason to expect it would be specific to males. That came as a complete surprise.”