Neuroscientists show that it’s possible to turn the volume down on a negative memory by stimulating other, happier ones.
Even though you may not realize it, each time you recall a memory—such as your first time riding a bike or walking into your high school prom—your brain changes the memory ever so slightly. It’s almost like adding an Instagram filter, with details being filled in and information being updated or lost with each recall.
“We’re inadvertently applying filters to our past experiences,” says Steve Ramirez (CAS’10), a Boston University (BU) neuroscientist. Even though a filtered memory is different from the original, for the most part, you can tell what that basic picture is, he says.
“Memory is less of a video recording of the past, and more reconstructive,” says Ramirez, a BU College of Arts & Sciences assistant professor of psychological and brain sciences. It is both a blessing and a curse that memory is malleable in nature. If we remember false details, it is bad. However, especially for memories of something scary or traumatic, it’s good that our brains have the natural ability to mold and update memories to make them less potent.
What if it’s possible to use the malleable nature of our memories to our advantage, as a way to cure mental health disorders like depression and post-traumatic stress disorder (PTSD)? Ramirez and his research team are actively pursuing this goal. And after years of studying memory in mice, they’ve found not only where the brain stores positive and negative memories, but also how to turn the volume down on negative memories by artificially stimulating other, happier ones.
“Our million-dollar idea is, what if a solution for some of these mental disorders already exists in the brain? And what if memory is one way of getting there?” Ramirez asks. In two new scientific papers, he and his team demonstrate the power of our emotional memories and how our experiences—and the way we process them—leave actual physical footprints on the brain.
Mapping Positive and Negative Memories
One of the most important steps toward using memory to treat memory-related disorders is understanding where positive and negative memories exist in the brain, and how to distinguish between the two. Memories are stored in all different areas across the brain, and the individual memories themselves exist as networks of cells called engrams. Ramirez’s lab is particularly interested in the networks of memories located in the brain’s hippocampus, a cashew-shaped structure that stores sensory and emotional information important for forming and retrieving memories.
The term “engram” was coined in 1904 by memory researcher Richard Semon. An engram is a unit of cognitive information imprinted in a physical substance, theorized to be the means by which memories are stored as biophysical or biochemical changes in the brain or other biological tissue, in response to external stimuli.
In a new paper published in Nature Communications Biology, Ramirez, lead author Monika Shpokayte (MED’26), and a team of BU neuroscientists mapped out the key molecular and genetic differences between positive and negative memories. They found that the two are actually strikingly distinct on multiple levels. It turns out that emotional memories, like a positive or negative memory, are physically distinct from other types of brain cells—and distinct from each other.
“That’s pretty wild because it suggests that these positive and negative memories have their own separate real estate in the brain,” says Ramirez, who’s also a member of BU’s Center for Systems Neuroscience.
The study authors found that positive and negative memory cells are different from each other in almost every way—they are mostly stored in different regions of the hippocampus, they communicate with other cells using different types of pathways, and the molecular machinery in both types of cells seems to be distinct.
“So, there’s [potentially] a molecular basis for differentiating between positive and negative memories in the brain,” Ramirez says. “We now have a bunch of markers that we know differentiate positive from negative in the hippocampus.”
Seeing and labeling positive and negative memories is only possible with the use of an advanced neuroscience tool, called optogenetics. This is a way to trick brain cell receptors to respond to light—researchers shine a harmless laser light into the brain to turn on cells that have been given a receptor that responds to light. They can also color-code positive and negative memories by inserting a fluorescent protein that is stimulated by light, so that positive memory cell networks glow green, for example, and negative cell networks glow red or blue.
Rewiring Bad Memories
Before the researchers label a memory in a mouse, they first have to make the memory. To do this, they expose the rodents to a universally good or unpleasant experience—a positive experience could be nibbling on some tasty cheese or socializing with other mice; a negative experience could be receiving a mild but surprising electrical shock to the feet. Once a new memory is formed, the scientists can find the network of cells that hold on to that experience, and have them glow a certain color.
Once they can see the memory, researchers can use laser light to artificially activate those memory cells—and, as Ramirez’s team has also discovered, rewrite the negative memories. In a paper published in Nature Communications, they found that artificial activation of a positive experience permanently rewrote a negative experience, dialing the emotional intensity of the bad memory down.
The researchers had the mice recall a negative experience, and during the fear memory recall, they artificially reactivated a group of positive memory cells. The competing positive memory, according to the paper, updated the fear memory, reducing the fear response at the time and long after the memory was activated. The study builds on previous work from Ramirez’s lab that found it’s possible to artificially manipulate past memories.
Activating a positive memory was the most powerful way to update a negative memory, but the team also found it’s not the only way. Instead of targeting just positive memory cells, they also tried activating a neutral memory—some standard, boring experience for an animal—and then tried activating the whole hippocampus, finding that both were effective.
“If you stimulate a lot of cells not necessarily tied to any type of memory, that can cause enough interference to disrupt the fear memory,” says Stephanie Grella, lead author and a former postdoctoral fellow in the Ramirez Lab who recently started the Memory & Neuromodulatory Mechanisms Lab at Loyola University.
Even though artificially activating memories is not possible to do in humans, the findings could still translate to clinical settings, Grella says. “Because you can ask the person, ‘Can you remember something negative, can you remember something positive?’” she says—questions you can’t ask a mouse.
She suggests that it could be possible to override the impacts of a negative memory, one that has affected a person’s mental state, by having a person recall the bad memory, and correctly timing a vivid recall of a positive one in a therapeutic setting.
“We know that memories are malleable,” Grella says. “??One of the things that we found in this paper was that the timing of the stimulation was really critical.”
The Quest for Game Changers
For other, more intensive types of treatment for severe depression and PTSD, Grella suggests that it could eventually be possible to stimulate large swaths of the hippocampus with tools like transcranial magnetic stimulation or deep brain stimulation—an invasive procedure—to help people overcome these memory-related disorders. Ramirez points out that more and more neuroscientists have started to embrace experimental treatments involving psychedelics and illicit drugs. For example, a 2021 study found that controlled doses of MDMA helped relieve some severe PTSD symptoms.
“The theme here is using some aspects of reward and positivity to rewrite the negative components of our past,” Ramirez says. “It’s analogous to what we’re doing in rodents, except in humans—we artificially activated positive memories in rodents, and in humans, what they did was give them small doses of MDMA to see if that could be enough to rewrite some of the traumatic components of that experience.” These types of experiments point to the importance of continuing to explore the clinical and beneficial methods of memory manipulation, but it’s important to note that these experiments were done under close medical supervision and shouldn’t be attempted at home.
For now, Ramirez is excited to see how this work can further push the boundaries in neuroscience, and hopes to see researchers experiment with even more out-of-the-box ideas that can transform medicine in the future: “We want game changers, right?” he says. “We want things that are going to be way more effective than the currently available treatment options.
“Hippocampal cells segregate positive and negative engrams” by Monika Shpokayte, Olivia McKissick, Xiaonan Guan, Bingbing Yuan, Bahar Rahsepar, Fernando R. Fernandez, Evan Ruesch, Stephanie L. Grella, John A. White, X. Shawn Liu and Steve Ramirez, 26 September 2022, Communications Biology.
“Reactivating hippocampal-mediated memories during reconsolidation to disrupt fear” by Stephanie L. Grella, Amanda H. Fortin, Evan Ruesch, John H. Bladon, Leanna F. Reynolds, Abby Gross, Monika Shpokayte, Christine Cincotta, Yosif Zaki and Steve Ramirez, 12 September 2022, Nature Communications.
This work was supported by the National Institutes of Health.
I’m curious where your ideas to heal through facing trauma in the ability to heal the damage due to the memory of the event may come from. If it is based off of any of the healing based modalities I have established over the years I would like the information that you obtained regarding my notes. You’re more than welcome to speak to me regarding the idea of healing PTSD as it’s something I’m currently establishing through years of work in the healing arts. I’m self taught like any other great mind known to brilliant works in new ideas. Nothing related to science or medical technology. Thank you
Tony Robbins has been applying this principle of “overwriting” negative memories with positive memories for decades already and literally with millions of people at his thousands of events. Amazing to see how the science is just now proving the validity of his techniques.
This is an amazing article. Speaking for myself. So much time is spent in our lives regurgitating PTSD memory. Only if victims of this diagnosis can learn from this study that the antidote for PTSD is simply using your positive memories of life. Did I get it right? Feedback please!!
I would hypothesize that this can work the opposite way as well. A sad event can also get worse in your mind the more you think about it. When something is “bad” you can make it worse by envisioning it worse and that can make you more depressed. This can also cause people to attempt to gain more sympathy which would also induce “happy” feelings from the sympathy thus entrenching those false negatives even further. I would hypothesize that you could even do this with false memories in such a way that you create an entirely false memory and get the the point were it is believed. All of these have massive social, legal, and political implications…. great article! Keep up the awesome work!
If a murderer has fond memories of murdering, where is this memory, stored?
What is the criteria that the body uses,and how does it correlate to morality?
Im betting, there is no correlation. I am betting that this is simply using emotions as an indicator, which is unreliable and dependent upon one’s worldview
Good day to you.
I am commenting today as I pray that this is going to be the solution to so much sadness and desperation and loneliness in this world. Depression is awful and it’s grip is strong! My brother in Concord Massachusetts was recently diagnosed with PTSD from something that happened at school. He is now 60 so it’s deeply ingrained.
At the same time, literally!!!! my boyfriend was attacked on the ocean by a rogue bull seal of 300+kgs affected by something similar to Red Tide and underwent nearly 3 hours of plastic surgery to repair 15 areas of his R leg. He is now 39 so age being in his favour he recovered well physically but over the months I have noticed things and my only answer is PTSD! Not surprising considering what he went through. But he won’t talk about it and if I say anything he gets angry with me. I have studied psychology but am a practicing hairstylist. I love my boyfriend enough to want to see this through and hopefully bout the other end as well! But I fear it’s getting worse with each week! The attack was on 16 May 2022 so almost 6 months has passed now.
His temper is chronic and flared out of no where.
He self isolates in the bathroom out of the blue for an hour at a time.
He has developed really bad skin problems mainly on his back… Over production of Cortisol?
He is completely insecure and very suspicious about everything. He will even say ‘you had 2
Oranges the other day and I only had one so that other one is mine.
So I say ok. Then he says why don’t I stand up for myself!
I was asked the other day if I am short of cash til I get paid then why am I asking him for grocery money when I can use my 2nd bank account and card! I don’t have one! Of either!!!
He has also been physically violent a number of times. Fortunately not too badly but enough to scare me shirtless and he didn’t care how he had made me feel.
When he finished work and we are together he can talk about his day for over an hour. If I say one thing about my day, one little comment I get my head bitten off cause I have been blubbering for nearly 2 hours and when is supper?
I used to argue the point but have given up as it goes nowhere..
He has become totally cold and heartless and really doesn’t care at all about anyone but himself!
That is not the man I met and fell in love with! He has been amazing from the moment we met! And always very loving and caring and considerate.
Now he says he loves me and I must have a good day and if we chat on WhatsApp during working hours he will say like I can fetch him at 4.30 if I am done at work and he lives me lots and lots and can’t wait to come home and chill.
He says it but he shows nothing!!!!
Since the 16 May 2022 I have had no affection at all bar a peck hello or goodbye! Not even a hug!
In mid 2021 this happened briefly for about 3 weeks and he was having a big problem with certain issues and he said it will be ok… he ‘just can’t when he is very stressed!’
Well!!! Warning bells went off then to a degree but it came right so quick that it went out of my mind!
This time like hello!!! On 16 November 2022 which is 15 days away it will be 6 months so right now it’s 5 1/2 months since he has touched me!
I did ask him once over a drink at a chilled time and he was calm and and and well!!! The answer was simple! I have changed!! I am not the Kathi he fell in love with! So best I change my attitude and also stop being so disobedient (he is 39 and I am nearly 59!!!) when he tells me to do something and then maybe he will feel something for me again!!!
Clearly I understood that he doesn’t understand why he is not getting excited to see me to be blunt but I am sure I don’t need to explain that one to any of you! So I said well I know I have put on a couple of kilo’s since we met but… and he but my head off shouting do I (me) think he is that shallow! I live you for what’s inside that beautiful person that caring loving woman who just happens to be very beautiful as well!
I cried bucket loads!!!! Because he said it so genuinely and so sweetly that for a few minutes I had the man I had fallen in love with back!!!!
By the time I had dried my tears the other guy was back and my beautiful lover was gone again!!!
And he used to love cooking! A total passion!
And live preparing everything for me after a long day!
Since well 16 May, you know the date by now he has not even made a cup of tea or coffee!!! Nothing!!! And he always said how much he enjoyed it! Well he does none of those things anymore so…Doesn’t even pick up his clothes does nothing!!!! And if I ask him he tells me when I start bringing in the same amount of money each month I can try again! I do! We earn pretty much the same!!!
Anyway because of all of the above I am pretty much convinced that he does have PTSD and he won’t acknowledge or talk about it have anything to do with any serious chats!
I am trying to find a way to slip a testosterone replacement in his food! Just to make him more loving! I don’t care if we don’t do the deed! I love it with him always been amazing!!! But I just want to be held and feel loved!!!
I have never been in a relationship with someone who is home with me every night and felt so totally alone!
So all the best with your continued studies and trials and etc etc etc and I shall live in the hope that I will receive an email from your end saying that he will be your first patient in your trial and will be free of charge! Being in SA we could never cover costs etc.
I love that the article starts by citing something from 1904 and the first 3 comments are like “I was first, see me.” Talk about zombie problems…
It worries me, that there is no discussion about the ethics in this paper. The ability to manipulate memories, alternating people’s understanding of the world and there for, a core belief about who they are in this world. How this can be misused for mistreating someone, and then alter the experience. At least not that this should be researched with great care.
EMDR healing technique does the same for PTSD. I hope science and spiritual healing get to as many as possible suffering people.