Manipulations of Memory

VGopinath's picture

 Neural and Behavioral Sciences Senior Seminar

Bryn Mawr College, Spring 2010

Manipulations of Memory

Memories are necessary to navigate the world and define ourselves.  We assume that our memories are accurate and trustworthy but scientific studies are repeatedly showing us that assumption is false.  If our brain is "lying to us," what are the implications of that on our understanding of our own experiences, history and self-identity?  Does this change our treatment and dealings with individuals with memory disorders?  Recent research has focused on way we can intentionally manipulate memories: to delete "harmful" memories, create or edit memories.  We are interested in investigating these techniques- psychotherapy, psychopharmaceuticals, cognitive behavioral therapy- and the effects of these treatments on society's perspective on memory.  

"It selects, eliminates, alters, exaggerates, minimizes, glorifies and vilifies also, but in the end it creates its own reality, its heterogeneous but usually coherent version of events; and no sane human being ever trusts someone else's version more than his own."  Salman Rushdie in Midnight's Children


Background readings:

Some relevant thoughts from last week:

Anxiety

Anxiety, like depression, may actually be helpful in certain circumstances ... If a person's conscious reality seems harmfully anxious then that is all that really matters ... mrobbins

To what extent do individual realities shape cultural reality ... and vice-versa? How variable is one's reality? ... kenglander

I think culture plays a huge role in the development of anxiety ... Bo-Rin Kim

anxiety is surely uncomfortable, but if we eliminate it it completely, we might induce more drastic problems in other areas. (If you block anxiety, as David said, you likely have a less motivated population - I think this obviously leads to a society that does not function as well) ... Sarah

it seems that it would matter whether the source of anxiety was based in a fear of social interaction as compared to a general fear of the unknown. But doesn’t this argument just lead us back into the conscious vs. unconscious discussion? ... EB

My main thought when presented with a situation like two different people have anxiety and one copes with it fine while the other has an anxiety disorder can only leave me with a few options for why this can be. Either there is a mutation that causes there to be less of a suppression in the person with the anxiety disorder or maybe the personality of the individual who copes with the disorder helps them to turn this negative into a positive ... Vadilson

Imaging

While fMRI may not give us an accurate portrayal of what brain regions are involved in certain behaviors, it gives us a starting point to investigate further ... Bo-Rin Kim

Can't we just calibrate the fMRI to any individual in the same way that the studies did to their subjects? And even the generalization across people does not seem, in principle, altogether impossible ... David F

While I want to agree that there is an "uncalibrateable and non-generalizable individual distinctiveness" that exists in each person, I am a bit confused about how scientists can arrive at that conclusion when they are using techniques that are supposed to be generalizable across subjects ... kenglander

Because imaging techniques look for areas of strong localized activity, it seems unlikely that fMRI would ever be able to detect a subtle and diffuse signal characteristic of recalling a particular memory ... LMcCormick

Discussion summary (David)

Anxiety

Our discussion began with a return to the concept of anxiety. Although anxiety is often viewed as a negative state, we considered its positive utility, and even entertained the possibility that anxiety could be integral to our very functioning. Much of this discussion was contextualized in terms of success and informed in large part by a finding that many CEO’s are more anxious individuals, raising the question: is stress a critical part of becoming successful?  Or in other words, could people be successful in the same way without anxiety? Some students affirmed this possibility, saying that mere planning does not seem to necessitate anxiety, and that this planning can be equally effective in accomplishing one’s goals. However, others felt that anxiety, or at least a form of discontentedness, plays a crucial role in driving someone to achieve lofty ambitions (e.g., Sara Berman’s example of Darwin exhibiting symptoms of depression).

In support of the possibility that anxiety does not play a crucial role in success, Professor Grobstein mentioned that many skilled animal trainers use only positive reinforcement: could purely positive reinforcement permit success without the stress of failure? Many students responded by considering anxiety-inducing effects of positive reinforcement, such as in the confusion required to achieve obscure, rewarded behaviors. Final thoughts included accounts of successful individuals without obvious signs of stress (e.g., the pilot who landed a malfunctioning plane in the Hudson River) and the possibility that stress covaries with other traits which themselves promote success (e.g., for CEO’s), suggesting that stress per se may be irrelevant to success. Professor Grobstein also commented on the peculiarity of the class’ ardor in defense of stress as a component of success.

Imaging

Much of our discussion on imaging hinged on taking seriously the possibility of fMRI’s capacity to “read minds.” We first discussed some practical hindrances to this use, such as the prohibitively extensive individualized calibration that must take place in order to read his/her thoughts. This led into a more fundamental discussion as to whether an fMRI could, in principle, read thoughts. One essential question that this discussion raised was whether there is a fixed relationship between a thought and a neural pattern. Perspectives that addressed this question ranged from a thought that several approaches might lead to a single thought (therefore precluding a 1:1 relationship between thoughts and patterns) and a thought that the constantly changing brain precludes any fixed relationship between a brain pattern and a thought. This latter idea was compared to the Mississippi River which, although a single entity, can inhere in an infinite set of variable physical manifestations.

Memory

Our discussion of memory began with the article on PKMzeta, a molecule that has been recently implicated in the process of memory. We first considered the ethics of studying this molecule, given its potential for abuse, and whether its potential benefits outweigh those risks. A distinction was made between researching a molecule and producing it pharmacologically. Given that many of the ethical questions hinged on the possibility of erasing a single memory, we then explored the biological feasibility of doing so. Although we articulated several ways in which one might block the formation/activity of PKMzeta, we decided that we needed to know more about it before speculating about its uses.
    We discussed the usefulness of understanding PKMzeta in the context of Alzheimer’s disease, and how a PKMzeta-targeting drug developed to the end of treating it might be abused by “normal” people. We also discussed PKMzeta in the context of addiction, and whether it could ameliorate the symptoms of addiction. Is PKMzeta implicated in procedural memory or “addiction memory” in the same way as other memories? Would disrupting it maintain symptoms of withdrawal and relapse?

We then transitioned into a discussion of EMDR therapy, and whether or not this is an option that should be taken seriously. We reviewed the data presented in the article regarding its benefits in comparison to CBT and nothing, and discussed whether these findings convinced us of EMDR’s usefulness. EMDR was compared to a placebo effect, which raised the question of its legitimacy and even the ethics of implementing it in the treatment of suffering patients

Our discussion then turned to déjà vu, and how its existence forces/allows us to break down the phenomenon of memory. Does it, for example, imply that there is a “tag” that accompanies an experience to signify that it occurred in the past? The phenomenon of déjà vu also encouraged us to consider the relationship/similarities/differences between memory and familiarity. One proposed mechanism was that familiarity functions as a template, and a consecutive sequence of familiarity produces a memory. Other discussed features of déjà vu included a seemingly necessary component of feeling startled, and how déjà vu might interact with consciousness versus unconsciousness. We also discussed the feasibility of déjà vu’s proposed mechanisms, which led us to question whether we have any “true” memories at all.

Continuing conversation in on-line forum below

Comments

Art Funkhouser's picture

Déjà vu is not a unitary phenomenon

It would seem there are many forms of what we might call "déjà experience", each, possibly, with its own etiology. I have tried to gather what information about these types of experience and make them available for those wishing to learn more about them: http://www.deja-experience-research.org . Those who have a few minutes to fill out an on-line questionnaire about their déjà experiences are encouraged to do so. The URL is http://silenroc.com/dejavu . Comments and suggestions about either of these websites would be most welcome. Anyone wishing to help out with the statistical data analysis from the questionnaire will be greeted with open arms.

Claire Ceriani's picture

That study with the blind

That study with the blind person is really interesting.  It hadn't even occurred to me that deja vu could occur without visual input, but of course it could, given the proposed causes we talked about.  I suppose it makes sense that the brain might occasionally get its sense of past and present mixed up.  We process a huge amount of information as we're experiencing it with our senses, and that triggers real memories.  The brain may sometimes confuse incoming information with recalled information, giving us the sense that we're remembering what we're currently experiencing, even though we also know that this experience is new.  I have to say that I honestly don't think I've ever had true deja vu.  I've had the experience of feeling like something is familiar, and then figuring out why it's familiar, remembering that something similar did actually happen and it's not unusual that I should be reminded of it.  But I've never felt like something is familiar when I know it shouldn't be.  I don't think I've ever had the eerie sense that something very specific has happened before.  I didn't realize that it was so common.  I wonder if the prevalence of deja vu is due to just how fast our brains process information.  It makes sense that if a lot of stuff is going on at once very quickly, minor mistakes would happen now and then.

mrobbins18's picture

Deja Vu

 

I am fascinated by the phenomenon of déjà vu and how it interacts with consciousness and memory. Déjà vu translates to “already seen” but what is interesting about this label is that sight is not even needed to feel this sensation. A case study done at the University of Leeds investigated how a blind person experienced déjà vu. This subject came to the university’s research center complaining of constantly re-occurring déjà vu. Researchers studied his condition by undoing a zipper while playing a particular piece of music; hearing a conversation while holding a dish in a cafeteria etc. These experiences triggered a sensation of déjà vu in the subject. This case study further debunked the myth that the images in one eye were delayed in arriving to the brain thus, inducing the sensation of having seen something before. Researchers plan to further investigate the underlying mechanisms of this mysterious experience via hypnosis based on their belief that déjà vu occurs when “an area of the brain that deals with familiarity gets disrupted.” This experiment will ask subjects to remember words then hypnotize them to forget them and then show them the same word again in the hopes of creating a sense of déjà vu.

 

Personally, I would argue that déjà vu is definitely both a conscious and unconscious entity It is conscious in the sense that déjà vu inherently involves a very capable memory. Without the ability of maintaining and categorizing memories in a highly organized fashion, there would be nothing to confuse the sensation of past and present from. You would always be in a constant state of is. Temporal placement of memories provides the basic template of what was. Deja vu occurs when the past and present somehow disrupt each other, either by an overly familiar unconscious cue or a subconscious overlap of coding patterns in the brain. Déjà vu is a conscious sensation triggered by unconscious predetermining temporal templates (our memories) clashing with a conscious sense of “presentness” in reality. Déjà vu illuminates the weakness of the brain’s illusion of permanent and true memories. This phenomenon supports the idea that each past experience or memory has a framework that is constantly being integrated and compared with the present and subsequently re-coloring the old memories or unconsciously veiling new experiences and memories.

 

Paul Grobstein's picture

memory, imaging, and beyond

Lots of interesting food for thought in the two subjects discussed in our Monday session (memory and brain imaging), and in the continuing conversation here.  Two related ideas that I want to think more about ...

"Memory" is not one "thing," but instead a bunch of interacting things, and may well be a process rather than a "thing" at all.  That has some interesting implications not only for thinking about human experience but also for thinking about how one does neurobiological research.

What is likely to be "recognizable" ("calibrateable") in brain imaging is only those things that qualify as "shared subjectivities" and so the interpretation of brain images will have many of the same interpretational issues as exist with language.  That has some interesting .... etc. 

Jeremy Posner's picture

Memory Enhancement and Legal Memory

 This was very briefly touched upon in class but it interested me so I’ll return to it.  The appropriateness of the general use of memory improvement drugs.  The scenario outlined in class was that a drug developed for the treatment of Alzheimer’s was found (as such a drug most likely will when it is developed) to have significant positive general effects upon memory.  A parallel was drawn between this hypothetical drug and the non-prescription use of ADHD medications to improve focus.  The most immediate issue in his situation is the safeness of the use of such a medication in this manner.  I am assuming here that the side effects of such a medication would be moderate, as would abuse potential.  I actually think that the use of cognitive enhancers either by students or by professionals is problematic due not to a fundamental inequality but due to inequalities driven by availability.  I don’t particularly like the competitive aspect of academic and professional life; but even within a competitive framework so long as supply isn’t limited it would be beneficial if such a drug were available.  My personal conception of my role as a student is that it is not my goal to better my fellow students, though that’s a large portion of how I am evaluated, but to learn as much as I can and that this may be a case where attempting to control use of such a medication and to prevent its use as a supplement for the healthy would lead to a similar situation as is currently the case with stimulants; those with the resources and determination of use them illicitly would find a way to find a supply, resulting in an unfair disparity. 

While I am not so uncomfortable with the knowledge that we depend upon an imprecise process in memory to function in day-to-day life (I think that we have adapted most of what we depend upon memory for in everyday life to the limitations of memory) I do think that legal faith sometimes invested in memory has been proven to be problematic.  Studies of the reliability of the memory of even victims of a crime suggest that, as was a theme in class, we remember less than we believe or are willing to admit.  The issues that psychology has suggested exist within the legal system, however, (another major one would be that juries often begin with a presumption of guilt, regardless of what they are instructed) extend beyond the unreliability of memory and would be a worthwhile class topic in their own right.  

rdanfort's picture

It is very convenient that

It is very convenient that some two weeks after our class, news breaks of research that claims to distinguish between individual memories using fMRI, reported here: <http://news.bbc.co.uk/2/hi/health/8556422.stm>.  As anyone who was present for our talk can predict, the study does not claim to have succeeded in analyzing memory content from brain activation data, but rather discriminates between memories that have already been recalled under fMRI.  That is, subjects watched a few short films, recalled them seperately under fMRI, and were later instructed to recall any one of the films.  This BOLD data was compared to the earlier recordings in order to determine which memory was being accessed.

As we discussed at length, the calibration step is really key to this process working.  It's still a neat trick, but not one that can extract any information not previously delivered in a controlled manner.  It is no leap to imagine that even more calibration would be required to even begin to analyze the content of memory recall data - any given memory has a wide array of elements that give it meaning, each of which is likely handled in a very individualized way.  Two people experiencing the same event are unlikely to view it with the same affect and almost certainly will not recall the same details.  With that said, there must be some translation of individual thought process into broadly accessible meaning, since we perform this task when speaking or otherwise communicating with one another.  It follows that the common content of thought - elements that are most easily translatable into speech or writing - might be somewhat accessible to us.  Still, defining what these common elements might be, finding broadly applicable correlates in the brain, and turning that information into meaning is very daunting, and unlikely to give more information than one might get through simple conversation.

Bo-Rin Kim's picture

Another thought....the two components of memory

Before reading the NYT déjà vu article, I never really thought about what components actually make up memories. I thought it was really interesting that they discussed how memories are made of two parts: the content of the memory and the feeling of recollection. Memories are not just thoughts from the past but also the feeling, the recognition that you are remembering something. In this sense, memories are as much of a sensation as they are thoughts.
Tying this back to the discussion of PKMzeta, does this protein block both the content and this sensation of recollection or does it just block one or does it just dissociate the two so that the “memory content” is not recognized as a memory? I think this raises new questions about what the PKMzeta molecule is targeting and how it affects memories to “erase” them.
 

EB Ver Hoeve's picture

Deja Vu before the label

 

As David already said, I think déjà vu freaks us all out so much because it does force us to confront our understanding of reality. I am intrigued by this idea of recognizing the experience of déjà vu and how it relates to our discussion of shared subjectivity and labels. How did you first learn what déjà vu was? When were you first given its title and told that the experience was normal? Once déjà vu is “explained” I think it normalizes our experience of it. However, before déjà vu became a labeled phenomenon for you, did you still experience it? I think, yes.  But I guess all I am trying to say is that I would expect that the way I experience déjà vu now (having a label for it) and then (not having a label for it) are actually pretty different.  Yesterday, I was on the tennis court warming up my serve and having a conversation with my doubles partner and experienced such strong déjà vu. But even IN the experience of it, I was telling myself, “no, you are just experiencing déjà vu, no big deal”.   I wish I remembered what the perception of the experience of déjà vu felt like, BEFORE the label. Did it remove me even further from reality?  Did it make me feel special? Isolated? 

 

aliss's picture

In class, we discussed the

In class, we discussed the possibility of erasing a memory with a simply injection of ZIP, a molecule that would disable the memory-inducing molecule PKMzeta.  Someone suggested that this could be achieved by asking the person to think of the memory, and then using the ZIP to disable the PKMzeta on the specific pathway where it appeared.  However, even if this process were to be effective in erasing memories, there would be no way to erase a single memory without affecting other memories.  Memory is not stored like files on a computer, everything in its place and easy to access with the right sequence of actions.  Memories are intertwined; one memory can recall another memory that you forgot you even had.  There are so many types of memory: your memory of your 10th birthday compared to your knowledge of the capitals of all 50 states compared to your ability to ride a bike.  Are all of these types of memories created in the same way, with the same molecules?  Are they all organized along the same types of pathways?  It seems to me that we are a long way off from being able to ever identify a single memory in the brain, let alone manipulate it.  At this point, I feel that we have very little to worry about in terms of people using ZIP-like drugs to erase memories of drug addiction or to torture prisoners, or PKMzeta-like drugs to increase memory while studying for a test.  Who is to say that an injection of PKMzeta while studying will only make you remember the information you're taking in and not the conversation that the people next to you are having, or the itch on your knee, or the smell of someone's lunch?  Although I feel that this molecule could be helpful in studying the ways that memory works, and how we form memories and how they are recalled, I don't think we know enough yet about any of these topics to be able to put it to any use.

Bo-Rin Kim's picture

Obstacles to selectively erasing memories with PKMzeta

What stood out to me the most from our reading and discussion about the kinase PKMzeta is that memory could be so dependent on one molecule. Prior to this discussion, I thought memory was based on several areas of the brain interacting together to create a reflective thought. However, the NYT article seemed to simply memory (or at least a significant part of memory) to this one molecule. My argument would be that even though we discover how to control the use of PKMzeta, we would still be far from selectively erasing memories because there must be other substances and brain structures involved in memory formation/retrieval that interact with PKMzeta. This is not to say that PKMzeta is not a good starting point for memory research, but I really feel like it is just the tip of the iceberg.

I also think it will be difficult to use PKMzeta to selectively erase memories because I feel like the same memory can be stimulated using several different routes in the brain. The same memory can be triggered by several different stimuli. Maybe when the memory is triggered by scent a different neural/cognitive pathway is used than when the same memory is triggered by taste or some other sense. Thus, unless PKMzeta is able to detect and block all these different pathways, a memory cannot be selectively erased.
 

LMcCormick's picture

Memory

Many people in the class agreed that thoughts most likely do not exist as reproducible patterns that can be consistently observed by an fMRI.  This made me question why we are so insistent that a particular memory exists as one clearly defined connection that could possibly be “erased”.  Isn’t it possible that memory exists as malleable and adaptable neural connections, making it impossible to target a specific memory?  According to the study, ZIP was able to make rats forget the experience of an aversive taste.  However, perhaps ZIP is not targeting a specific memory in this case, but rather erasing entire segments of the rat’s memory.  Of course there is no way to know, because we can’t ask them.  It just seems odd to me that we can talk about thoughts as malleable and diffuse signals in the brain, while we assume that memories consist of concrete connections.  Additionally, I think it is critical to acknowledge the point – which several people have mentioned – that a specific memory is intertwined with a multitude of other memories and related experiences, which complicates any potential use of ZIP.

           

            In addition, I think that the ethical implications of the use of PKMzeta and ZIP are important to consider.  Some people compared the illegal use of PKMzeta to the illegal use of Riddlin.  However, I feel that the impact of being able to enhance memory is much more profound and dangerous than being able to increase attention span.  One can easily argue against this claim, but I feel that one’s intelligence is mainly defined by their memory (ability to recall facts, remember how to solve a particular problem, etc.) and ability to think critically/problem solve.  If you agree that memory is a critical component of intelligence, then the use of a drug that enhances memory seems like a huge problem.  Why wouldn’t you take a drug that makes you smarter??

 

kenglander's picture

manipulating emotion, not memory?

Like Megan, I agree that it seems difficult to erase and manipulate memories when they are already incredibly variable in the first place. If we are constantly reshaping our memories, then how can researchers attempt to completely erase it? This question seems especially relevant to episodic memory since that could imply erasing large chunks of one's autobiographical memories.

What if ZIP permanently manipulated memories rather than completely erased them? Granted, the brain already manipulates memory to a certain extent, but the emotions can be relatively consistent. Patients with PTSD, for example, might recall certain experiences (i.e. a particularly violent battle) with slight variation to the dialogue or people's facial expressions, but it is unlikely that the grief or anger associated with the situation will become happiness or pleasure. I'm not suggesting that we should make a drug that causes a complete reversal of emotions, but what if we had a drug that manipulated the emotions associated with the memory (i.e. instead of guilt there was a feeling of neutrality)? Perhaps learning to separate the emotions tied to the memory is related to other therapies and could help us understand how/why CBT and EMDR work.

Aside from the obvious obstacles this drug would have to overcome (for starters, researchers would need to figure out how emotion and memory are related and how emotions are manifested in the brain), I think this raises a lot of ethical issues; should researchers be able to regulate how we feel about certain memories? That is, who decides which memories/emotions warrant psychopharmaceutical interventions? Should it replace other therapies such as CBT if it has the same success rate (and what effect would that have on how we decide to treat psychological disorders)?

vpina's picture

memory issues

In reaction to the memory-erasing drug it would seem highly difficult to find the exact memory that someone wanted to erase. Though I believe there is a connected sequence for each particular memory even if it changes at all times I don’t think there could be a way to find that sequences and erase it before it changes its pattern. With that there is a major chance that unwanted memories would be erased. Also it doesn’t seem likely that when erasing an addiction connection that this would take away the chances of readmission. To do this the memory of the people they were surrounded around and other atmosphere memories would also have to be erased and if this was done than how much of the person is actually left? Though this is an area that should be researched I don’t think it would make sense until we had a better understanding memory and how it works overall.               

Sasha's picture

The notion of defining

The notion of defining ourselves through our memories- "our memories are what form who we are"- was an interesting idea that was brought up during our last discussion. Do we define ourselves through our memories? If we do define or identify ourselves through our memories, then that would imply our identities are constantly changing. In particular, if we agree with the notion that we "wipe our memories out every night and reconstruct our memories every morning" then perhaps our "identity" changes in the same pattern? While I do believe that our identities change over time as we grow and experience new things and the learning process and development of new memories certainly impacts how we see ourselves, or at least how I see myself, I am not sure I feel as though our identities change every day as our memories are reconstructed. How we "define" ourselves is perhaps a more draw out process that changes over months and years. So, to a great extent our memories are involved in creating our identities, but there must be something else, something more concrete than our memories, that allows us to wake up every morning and not constantly question who we are and what we're doing since our memories were wiped out and reconfigured during our sleep. For some reason this question of "memories forming who we are" is particularly challenging to me. I guess I'll see what I think in the morning.

I think I remember reading some clinical stories from Oliver Sacks dealing with memory and identity. I'll see what his patients can teach us...

sberman's picture

PKMzeta possibities

 Since class, I have been thinking a lot about how we could practically use ZIP as a means to erase memories. It seems plausible to me that an individual could be asked to recall the particular memory to be erased, and that by administering ZIP, this would deactivate the pathways involved in recall of that memory. This method, however, necessitates that each memory have a distinct pattern/pathway of neurons activated in the brain. --> this is not unlikely because otherwise, how would different memories manifest themselves differently in terms of what we experience?  A possible major roadblock, however, is that at least some of the neurons involved in the recall of one memory are likely be involved in the recall of at least some of our other memories. I do not see any way in which this overlap issue could be avoided. (If this overlap phenomenon did not occur, new connections would have to form every time we created a memory). If the pathways involved in one memory were knocked out, this could potentially lead to the erasure or altering of other memories. Now, not only are a few painful memories erased, but a person's sense of self could be irreparably destroyed (if we agree a person is defined by their memories). 

I agree with the fact discussed in class that studying PKMzeta/ZIP is an ethical slippery slope. If this drug was able to selectively target memories or even groups of associated memories, who's to say that the drug would not be abused? However, I feel that by completely halting research on PKMzeta/ZIP, we would be doing a great disservice to those that ZIP could possibly help (PTSD and addiction sufferers). As scientists, it is our duty to determine the risk-benefit payoff of studying something that could potentially be used in a harmful way or have negative effects. In terms of PKMzeta, I believe that the information we would gain about memory recall would take precedence over the possible abuse of ZIP/ZIP-like drugs. Especially at this point, where we are not even sure that ZIP could erase a particular episodic or explicit memory, I think it would be premature to stop studying PKMzeta now. I'm not saying that scientists would not be responsible for helping to enact safeguards against abuse of such drugs. Rather, I assert that the scientific community should not ignore a molecule that could potentially alter the study of the science of memory.

David F's picture

Deja Vu

I was very intrigued by our discussion and the article on deja vu, particularly in how the phenomenon forces us to consider the intersections between memory, familiarity and waking experience. It seemed to me a plausible explanation that deja vu signifies the temporary dissociation between the "memory trace" or "information content" aspect of an episodic memory and the "accompanying experience of recollection." This latter aspect could serve as a "tag" that denotes an experience as occurring in the past, and which if errantly applied to present experiences could give the sensation of deja vu. I wonder if this theory of deja vu is compatible with a theory constructed in class regarding memory. Professor Grobstein suggested that familiarity may serve as a functional "template," where perceived objects and situations, when appropriately matched to these templates, appear as familiar. If we perceive several features of our experience as familiar in a consecutive sequence, we may apprehend that experience as a memory, perhaps even startlingly so. Does this theory incorporate an idea of a misplaced "tag"? Perhaps that tag could be understood as the quality of an experience that contains a sequence of familiar events and objects. Thus, the misplaced tag in deja vu would more fundamentally reflect an over-reactive familiarity module, perhaps due to overly lax templates. 

Regardless, it's apparent from these vague and metaphorical theories that the concept of deja vu is difficult for us to wrap our heads around. Deja vu incorporates a slew of problems regarding our very understanding of reality. Perhaps one of the most disconcerting issues concerning deja vu is how vivid or "immutable" the sensation appears to us. When we experience it, we KNOW that we have perceived our current sensations before. And yet we haven't. Maybe even more poignantly than what deja vu says about the dissociation of memory is what it says about the vividness of our experience. If we can't trust absolute lucidity, what can we trust? In the article, Moulin says that "'It's an immutable feeling, but it's not immune to reason," but I wonder to what extent this is just something easy to say when speaking about treating patients other than ourselves.

meroberts's picture

Can memory be manipulated?

Can memory be manipulated? Clearly, a memory is manipulated every time it is recollected. We remember what we want to remember. We can suppress memories and we can create false memories. There are an infinite number of ways to manipulate a memory. But, in terms of the scientific method, how can we successfully manipulate memory when it is already so variable? Shouldn't we be able to control the variable being manipulated? This is exactly why I don't think science will ever be able to target specific memories for eradication. In class, we discussed the possibility that memories could be erased, as in the movie The Eternal Sunshine of the Spotless Mind. But how would these memories be targeted? Until other molecules are identified in long-term potentiation, the long process involved in making a memory, no one will ever be able to isolate memories from other memories.

Our class reading involved an article about "editing memory" with the use of a targeted "memory molecule", called protein kinase Mzeta (PKMZeta). The article about PKMzeta described where PKMzeta was found to be most prevalent. PKMzeta settles in "the fingerlike connections among brain cells" that have been involved in the process of creating a memory. Thus, PKMzeta may be involved in the connections being made between neurons to create the memory, but this process is the same for every memory ever made. There is no way that one group of connections between neurons can be differentiated from another group of connections between neurons. For this reason, I don't believe that memory can be edited. I think it would be really interesting to determine what processes are involved in the creation of false memories. How would these connections be similar to, or different from, the connections involved in a "less-false" memory? Would PKMzeta still be involved? Also, what role does consciousness play in what we remember, as well as in the process of remembering- whether it be explicit or implicit memory. How does consciousness affect the connections made between neurons during long-term potentiation?

VGopinath's picture

PKMzeta and ZIP

 

      In our discussion last night about PKMzeta, we definitely needed some more scientific information on this molecule and ZIP, its inhibitor, so I looked up a few articles (links to them are below) that can hopefully inform our conversation.  

     According to Serrano et al. in a Dec 2008 article, protein kinase Mzeta (PKMzeta) is necessary for long-term potentiation.  While we don't know what type of information is encoded by the kinase (I imagine they mean which neuronal connections are strengthened by the presence of PKMzeta), we do know that it plays a role in aversively conditioned associations, which can be was eliminated with ZIP.  According to Dr. Sacktor's Science report, ZIP was microinfused into the Insular Cortex.  They were testing taste memory and the gustatory cortex is located in the IC therefore it's a logical choice for where to locally administer the drug.  Other interesting aspects they studied that weren't mentioned in the NYT article are that ZIP acts within two hours, at most.  The rats were also tested over time to see if the effects of ZIP are transient but they found no evidence of memory recovery.  Neophobia is an aversion to new stimuli so the researchers gave rats a new taste repeatedly until they were used to it and were no longer repelled.  After ZIP administration, those rats displayed aversion to the new taste as if they had never tasted it before.  This is interesting because they thought that this memory could also be stored in the hippocampus and is not the same type of association they were testing before, in which they were confident about the IC as a ZIP target.  They also tested rats with two different associations and ZIP disrupted both of them.  

     I think the last point about the lack of selectivity of ZIP may be a critical problem when thinking of applying this drug to humans.  We would need to find a way more specific than simply targeting the IC to prevent loss of necessary aversively conditioned associations.  

     The more recent articles cite persistent PKMzeta activity in both unpleasant and rewarding associations whereas earlier studies just looked at aversive long-term memories.  While Sacktor administered ZIP to the IC, Serrano looked at multiple locations in the brain, including the hippocampus, where spatial memory  is stored.  This study found that accurate, precise spatial memory requires PKMzeta but more global spatial information in a search strategy (tested using a water maze and an eight-arm radial maze) was not significantly impaired by PKMzeta.  The contrast among the types of memory and information requiring active PKMzeta could enhance our understanding of memory in general, as well as ways to treat memory disorders, especially those with "incorrect" associations, like deja vecu, Alzheimer's etc.  These more recent studies have also demonstrated how far away we are from using this drug to selectively erase painful or specific memories.  We clearly are a long way from Eternal Sunshine of the Spotless Mind or the flash of light from Men In Black.  

 

http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.0060318

http://www.sciencemag.org/cgi/content/full/317/5840/951

 

Techno Music's picture

Manipulations of Memory

I don't feel our brains ever "lie" to us, but rather, it is possible that some things, whether consciously or subconsciously, are better forgotten.

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