Comments for Disambiguating the similar since 1971 Thu, 30 Jan 2014 18:08:41 +0000 hourly 1 Comment on Questions and Answers by Michael Hunsaker Thu, 30 Jan 2014 18:08:41 +0000 I think what makes the hippocampus is special is twofold. 1) Spatial pattern separation / completion. If the models are correct and the DG is involved in generating contextual representations, then it is really cool that the DG makes space and then orthogonalized it! 2) I think the hippocampus is involved mostly when one has to make flexible use of orthogonal representations to perform a task. That is, when there is a short term memory (or working memory in the Olton sense of the word) component to the task. For example, Ray Kesner just demonstrated that the ventral dentate gyrus is important for pattern separation for odors when (and only when) a 60 second delay is interposed. There is no DG requirement at a shorter delay of 15 seconds.

I do think the whole brain does work as a sort of pattern separator–it would be a sign of poor design id the brain were not designed to store vast amounts of information that were overlapping and not helpful for behavior (i.e., escaping predators, finding food, etc). That is why I am endlessly fascinated by the pattern completion processes in CA3…they seem to be the solution to a necessary problem with how the brain encodes information, meaning the tendency to over-orthogonalize.

Comment on Questions and Answers by Michael Yassa Tue, 14 Jan 2014 05:37:09 +0000 OK so first I have to admit I haven’t been on here in a long time. Things have been busy. But I just realized that no one took you up on the “free answers for your questions” invitation. I would have jumped on that. That being said, I don’t consider myself an expert at all on these issues and do have a question that I hope you and others can help me think about. We talk about pattern separation as something that the hippocampus is really good at but it also happens outside of the hippocampus (for example in olfactory cortex, entorhinal, perirhinal, etc…) but if it’s so ubiquitous and happens pretty much anywhere there is any input/output transformation that decreases similarity… can we think of it as a function of the nervous system in general? I’m thinking about some of the data from the attention/perception world where they see thresholded discrimination functions in pretty much any hunk of cortex they test. Decision-making folks find the same thing and talk about it in terms of action selection… These functions seem like they’re popping up everything.. Is this simply how we can make sense of the world around us? And what makes the hippocampus special is the fact that it can access the most hyper dimensional input?

Comment on What do we mean when we talk about pattern separation of stimuli anyways? by Michael Hunsaker Fri, 13 Sep 2013 20:11:28 +0000 So after a bit of a break I came back to the site with another question, but I think I will just posit it here as it fits as a comment under my post.

Is anyone interested in identifying, standardizing, and feeely posting under CC licensing actual sets of experimental stimuli for Human, primate, rat, and mouse experimentation.

I am wondering this since I was casually reading a paper of Craig’s wherein they parameterized stimuli to generate functions of discrimination across stimuli. I was actually very pessimistic with regards to the human pattern separation tasks prior to this paper since I worried about the difference between degraded and partial cues and how pattern separation and completion would be preferred bases on the cue type.

For rodents, I know Tim has done work with the touchscreen task development that is translatable across labs. But the feature ambiguity stimuli Ray and I have used in rats and mice have by and large not been parameterized to generate functions similar to those observed in the human research. I just wonder how important this is to standardizing results across labs in some way.

Comment on Pattern separation: What’s the problem?! by Michael Hunsaker Fri, 13 Sep 2013 19:58:40 +0000 I wish no one has ever said that! I remember vividly when I was very guilty of imprecise language that was along these lines.

The manuscript was one wherein we lesioned dorsal and ventral CA3 and dorsal and ventral CA1 and compared the behavior of the animals on fear conditioning tasks.

We stated (I stated as I wrote the paper), that ventral CA1 learns… Whereas dorsal CA1 learns… And continued down that line for the behavioral results. I felt the reviewer was being pedantic at the time, but later realized they were right when they demanded I say instead that …animals with CA1 lesions were unable to perform…

It was an important lesson and I, to my knowledge, have always used more precise language in my manuscripts ever since. As far as I am concerned, this reviewer did me a great favor by teaching me this clear lesson.

I think Brad is right to ask that we use more precise language to describe what we are testing rather than using pattern separation or pattern completion as a catch all term to describe poor behavioral performance.

Comment on Pattern separation: What’s the problem?! by Brad Aimone Fri, 13 Sep 2013 14:13:01 +0000 From my computational perspective, I think the statement is fine; but really I don’t know if it is necessary (or maybe should be necessary). I think everyone recognizes that there is a distinction between computational concepts and behavioral tasks.

What I would like to see is a recognition of something along the lines of the community recognizing that computational theory can show sufficiency, but almost never necessity (in a biological context), and behavior can show necessity, but almost never sufficiency. This works for both regional assignment of function (the dentate gyrus is needed to do pattern separation and is sufficient for pattern separation) as well as linking computation to behavior (pattern separation is necessary to do X behavior, as well as pattern separation is sufficient to do X behavior). There is a tendency of people on both sides to be a bit, shall we say, “sloppy” with their descriptions, and I think this leads to the frustration. And given that the behaviors and the models are NOT the same, one cannot simply combine the necessity from one and sufficiency from the other.

Put another way, if as a behavioral neuroscientist, conclusions were limited to “this region/process is required for this behavior to occur” as opposed to putting up a final figure with big headlines saying (young neurons -> Pattern separation; old neurons -> Pattern completion; we can all go home!) based on a single experiment, I think people would be happier. Not that anyone has ever done that particular example.

Comment on Pattern separation: What’s the problem?! by Michael Yassa Wed, 11 Sep 2013 17:21:56 +0000 Tim.
No problem. Was nice to exchange in person at EBBS and I’m glad that one of the first public venues where some of the ideas on this board were discussed was that successful.

I’m curious though as to whether other folks on this discussion board can comment on this approach as well. Does it suffice to have a statement such as the one quoted by Tim above when discussing behavioral tasks and behavioral data? Do we believe that this would remove the confusion and immunize against misguided interpretations of our collective work? If not, what else should we be doing?

Comment on Pattern separation: What’s the problem?! by tim bussey Sat, 07 Sep 2013 17:44:56 +0000 Thanks Mike. Have already added it to an article in proofs and one in revision!

Comment on Pattern Separation – What’s the problem?! Part 2 by Zach Reagh Tue, 03 Sep 2013 21:20:17 +0000 I suppose I’ll lend the voice of a lowly rising second year PhD student! As a relative rookie to the concept of pattern separation and all the baggage it may or may not carry, perhaps it will offer a different sort of perspective.

I can most certainly appreciate the need for rigor in defining and applying terminology. In light of some recent work, it does seem that ‘pattern separation’ has taken on something of a buzz-word status, and that it’s being used in ways that deviate in varying degrees from its intended purpose. This seems most obviously problematic for purely behavioral studies that make strong and direct neurobiological or neurocomputational claims in the absence of…well…any neurobiological or neurocomputational data.

However, I tend to agree with Craig that avoidance of a term because of a potential for confusion is not the answer, and may actually be a hindrance to what otherwise amounts to perfectly good science. I think that a more reasonable approach is to take caveats for what they are, and recognize that certain approaches simply necessitate them. Perhaps ‘pattern separation’ is not the most kosher term to use in the absence of neurobiological correlates, but provided that such correlates are reasonably established in a given line of research, it’s acceptable (in my humble opinion, of course) provided that the authors make their intent in using the term as clear as possible. Simply put, we may gather the eagerly-awaited direct evidence of transformationally orthogonalized input as it passes from LEC/MEC to DG/CA3 to CA1, but we then have to make yet another series of computational leaps that bring this information to behavior. It seems that an overwhelming amount of data is consistent with the assumption that the DG is especially suited to undertake pattern separation (though certainly it occurs elsewhere in the brain to various extents, which I doubt anyone would deny), and we have a plethora of behavioral findings that are perfectly consistent with this. It will certainly be helpful to consider the respective inputs from the LEC and MEC to the DG, as has been done in several animal models, as well as the outputs from the DG. Certainly, we ought to exercise caution in terms of how strongly we make our claims in the absence of established black-and-white fact, but this applies to quite a large proportion of neuroscientific research. If the shoe fits, I see little harm in discussing things in terms of pattern separation (or pattern separation very likely having occurred) provided that we openly recognize the limitations of a given study and agree upon a set of reasonable standards.

There’s something to be said for avoiding operating over fallacious logical inferences. On the other hand, as several posts have pointed out, these fallacies are not necessarily so widespread (and don’t themselves necessitate that the conclusion was false). I do think that our field out to expect logical points to be made in publications. However, we also ought to bear in mind that there are certainly many of us who make every attempt to be as transparent as possible about our assumptions and what they mean in terms of the conclusions we draw, and temper them accordingly. As a (hopefully) up-and-coming student, I would really hate to poke my head up in the middle of a witch hunt =)

That’s my two-cents, albeit longer-winded than I’d intended. The discussions on here thus far have been very interesting and at times pretty eye-opening. What I would really find useful is, as I alluded above, some sort of agreement on a reasonable set of standards, be they experimental or terminological, that can get us all on the same page (or at least in the same paragraph).

Comment on What do we mean when we talk about pattern separation of stimuli anyways? by Michael Hunsaker Tue, 03 Sep 2013 18:48:46 +0000 I agree entirely with Brad on this one. Having recently done some work with the MEC and LECand processing distal space and proximal objects, it is tough. Particularly since the LEC = stimulus/object/proximal… (whatever we choose to label perirhinal inputs), and MEC = space, context, distal…(whatever we chose to label postrhinal/parahippocampal gyrus inputs) are not so clear cut. Ray and I found that the MEC and LEC do mostly what we say they do, but they also share some of the function of the other entorhinal areas.

A few years back at the Winter Learning and Memory Conference in Utah Pierre Lavenex and Menno Witter took us all to task, quite loudly inf act, that we have a very annoying habit as experimentalists of oversimplifying our systems so that we can use an easy explanation. I think Brad (and to some degree Adam as well) are raising great questions that we need to find some way to address.

Comment on Citation analysis by Brad Aimone Tue, 03 Sep 2013 18:09:23 +0000 It may be worth doing a similar analysis on Google Scholar as opposed to pubmed, as Google will often be able to return documents who used terms inside their papers that may not have appeared within the abstract or key words. I mention this because the phrases “pattern separation” and “interference” and even some notable figures based on that premise started being bandied about in 2004-2006, which is kind of a dead zone in your analysis above. I believe that one difference was that in those early years of neurogenesis function work (prior to the Leutgeb study a few years later) while the DG was thought to have a strong pattern separation property/feature, that wasn’t generally considered its sole function, at least not in the Treves / Rolls, O’Reilly / McClellland or McNaughton / Morris computational frameworks.

Comment on Pattern Separation – What’s the problem?! Part 2 by Michael Hunsaker Sat, 31 Aug 2013 02:44:19 +0000 One quick point here that bears mentioning and was actually the reason Ray and I wrote our review. The DG does not engage in pattern completion as defined.

If the DG does not engage I pattern. Separation or one reason another, that is lack of pattern separation. Not pattern completion.

For pattern completion, it is likely that a prominent but not talked about nearly enough pathway from the perforate path directly to CA3 is sufficient to provide a cue to guide retrieval, and particularly important for providing the partial cues to guide pattern completion. This was an idea elegantly discussed by Alessandro Treves and Edmund Rolls in 1992 and has since been critical to their models.

Additionally, and this is important for how the DG does not always dominate and thus we only pattern separate, the CA3 pyramidal cells’ spike 2-4 ms earlier than DG granule cells to pp stimulation. Brian Derrick has shown this for both MPP and LPP Stimulation in vivo.

As such, the DG does not play a role in pattern completion. In fact, based on the models, it cannot play a role due to the competitive inhibitory network that has been proposed to underlie the actual performance of the pattern separation process.

Just my two cents on this topic since we need to be careful not to misdeed e pattern completion. Especially since we are trying to prevent mis defining pattern separation.

Comment on Pattern separation: What’s the problem?! by Michael Yassa Fri, 30 Aug 2013 19:51:48 +0000 Tim,
This paragraph makes me oh so happy. I have started to use similar paragraphs in my papers as well and think it is excellent practice, so as to eliminate any potential confusion and not overstate the bounds of behavioral tests.

You have my vote.

Comment on Pattern Separation – What’s the problem?! Part 2 by Michael Yassa Fri, 30 Aug 2013 19:50:10 +0000 I don’t disagree that car-parking is not exactly process-pure but I don’t think that was Tim’s intent from this example or anyone else’s for that matter. Just wanted to clarify that and defend the use of such an example as I think it exemplifies scenarios under which pattern separation might be a helpful thing!

And I will take this opportunity once again to voice support for trying to understand what exactly it is that MEC/LEC are doing in service of encoding experiences and how do their computations affect downstream DG pattern separation. I think this is a critical avenue to investigate (and not just because we’re doing it) and hope that there’s a confluence of data both from humans and animals and across several different approaches and techniques that begin to speak to this in the coming years. This will significantly improve our understanding of how the DG encodes conjunctive representations.

Comment on Pattern separation: What’s the problem?! by tim bussey Fri, 30 Aug 2013 13:41:01 +0000 Thanks Guys, It sounds like we may be approaching a solution whereby we can remain rigorous in our definitions, while at the same time keeping the work at different levels linked together by at least some key words. I am very keen to modify my behaviour to help this happen.

Using my own stuff as an example, I am thinking I could write my papers more or less as I have been, but when using the term pattern separation (*) provide a footnote or similar to make definitions clear. (And not appear ignorant!) How about this:

“(*) We are aware the term ‘pattern separation’ refers, in the original computational literature, to a specific proposed mechanism involving the transformation of an input representation to an output representation, in which the output is less correlated than the input [words stolen from Jim], resulting in non-overlapping stimulus representations (refs). Our behavioural tests assess the use of such representations. However it should be emphasised that our tests do not assess the mechanism of pattern separation, as defined by the computational modellers (refs), directly.”

What do you guys think?!


Comment on Pattern Separation – What’s the problem?! Part 2 by Adam Santoro Fri, 30 Aug 2013 12:03:55 +0000 I don’t know if I necessarily take issue that pattern separation is needed for these tasks. I think that pattern separation, as a neural mechanism, definitely underlies memory interference tasks. But I also think it underlies all sorts of other behavior, and that it occurs in many regions throughout the brain. So my stance isn’t so much that memory interference doesn’t entail pattern separation, it is that we don’t know how much pattern separation in the DG, if it is occurring, is actually contributing to behavior in these tasks.

Also, as stated in another post, pattern separation in the DG is reducing the inputs from the MEC and LEC. We don’t know how memory interference tasks manifest in population activity in the MEC/LEC, and exactly what sort of information processing the DG is accomplishing by separating the incoming info. What kind of information does the MEC/LEC hold in these tasks, and how is this information transformed via separation? The theory is that it will manifest behaviorally as reduced interference, but I think there are so many unknown aspects (and known intricacies) of DG function that we can’t really isolate pattern separation in the DG as causing reduced memory interference. I think it also gets a little bit tricky when you consider the pattern completion mechanism occurring in the CA3 – how does the DG’s input to the CA3 influence pattern completion, and what is actually occurring to population activity in both regions during these tasks? If the DG ultimately separates population activity input caused by 2 similar stimuli, but the CA3 exhibits highly overlapped population activity due to pattern completion, then what is the DG doing, and how does this manifest behaviorally?

Also, kind of as an aside technicality, but I think the car-park example can also have some contributions from simple “forgetting” in addition to any potential effects of pattern separation…especially since the assumption for pattern separation would be that the person successfully remembers each spot in which he parked, and is able to parse them day by day. The actual situation would be a forgetting of the previous day’s car location, and selective memory of the present day’s car location. Thus, not strictly “pattern separation,” per se.

Comment on Pattern Separation – What’s the problem?! Part 2 by Michael Yassa Fri, 30 Aug 2013 04:48:56 +0000 Sorry if this is backtracking a bit, but I’m still catching up on all the posts. Adam takes issue with Tim’s example of where pattern separation is necessary. I think this may be a bit misplaced. Tim’s definition and indeed the example he offers is one that I as well as many many others have used in the past to describe pattern separation. It is not simply a discrimination procedure. It is a discrimination under conditions of interference that must be minimized. I would argue that such a situation does require pattern separation (cf the definition I used on the front page for what I mean here). Rate remapping is but one type, sensory discrimination of similar may be another. I think that Tim and I tend of think of separation as a much more universal phenomenon that happens across systems all the way from sensory to higher cognitive but vary in the mechanism and the information content.

So I’m not sure Tim’s example is not a valid example of where pattern separation is needed. There is interference that needs to be minimized. Where it is minimized and what mechanism exactly is something we can ask, but the definition of PS doesn’t include either rate remapping or dentate gyrus in it, remember? As long as overlap in input exceeds overlap in output, we call it separation. I don’t see any possible scenario under which minimizing the car park confusion wouldn’t require this particular algorithm to some extent. May be there’s something I’m missing in the argument.

If Tim’s description said that car park confusion can only be reduced by having DG pattern separation, I might take issue with it, but I don’t think either Tim or anyone else can make that claim strongly absent data with a car-park confusion experiment!!

Again, too late in the evening so if I don’t make any sense, I apologize.

Comment on Pattern separation: What’s the problem?! by Michael Yassa Fri, 30 Aug 2013 04:02:40 +0000 To address Craig’s point about Jim’s definition, I think the problem is that it is almost fait accompli for many papers that pattern separation occurs in the DG, and while all of the data thus far are consistent with this account, the critical test is the one Jim proposes, an investigation of how much transformation of the input has actually occurred.. impossible to do without measuring the input. I think this is a problem because many editors and reviewers are so convinced that PS occurs in the DG (given the statements mentioned in papers across the board), they don’t seem to understand that this critical test has not been passed. So if someone proposes to do this as “the nail in the coffin” so to speak, there may be a “so what?” attitude that is due to the perception that this is either (a) already established or (b) not necessary. There is something terribly wrong with that.

Now onto the bigger issue at hand: I honestly don’t think there’s a problem in overuse of the term. I like using the term although I do tend to use it to describe the computational phenomenon and then everything else is “consistent with” said computation. I think it helps aggregate our literature under the same keywords which is helpful as has been previously mentioned. I wouldn’t want to censor anyone’s use of the term or tell people they can’t say the word, but it would be good to get our definitions and facts straight. It is a fact that PS in the DG has not yet been demonstrated. We have evidence for signals consistent with this account but absent the critical test, it still leaves something to be desired. This is important for folks to understand when they write about the process, so that its occurrence in the DG is not taken for granted, and thus the extension to neurogenesis for example would require a little bit more of working through the logic as opposed to the oft seen: pattern separation = DG, DG = neurogenesis, therefore pattern separation = neurogenesis.

I think the issues that we’re complaining about are not unique to our subfield in particular, but we have the strong advantage that we’re all talking about this now before the literature on this topic explodes. The subfield is small enough right now that we get to decide how to shape it. If we demand more careful definitions, so be it. If we demand certain caveats to be acknowledged, so be it. I just wouldn’t want this exercise to put a damper on anybody’s research efforts or make anyone think they shouldn’t use the term at all. All we’re saying is that the use of the term should almost come with a license of understanding the meaning and the caveats.

So my take on this is that we should just make sure that our papers always have operational definitions for whatever it is we’re talking about: hardly a novel requirement for scientists. We’re working on “emotional pattern separation” for example as one of our newest extensions and looking at amygdala-DG/CA3 interactions. You might wonder WTF is “emotional pattern separation”??? Well, I can tell you we have a very clear operational definition for how we’re defining these signals (you’ll have to read the papers when they come out to see if you agree or disagree). I could have called it “!$@#%$” for all I care, and as long as I define what I mean by that, everyone should be OK with it. I guess I’m less concerned about the misuse/overuse of the term and more concerned about appropriate operational definitions.

So as an author in this space, I promise to always have these definitions loud and clear in my papers. And I can tell you that as a reviewer of papers in this space, this is what I require. So if Craig wants to use “behavioral pattern separation” but he defines it in terms distinct from the neural or computational definition that would be fine with me.

My “it’s entirely way too late in the evening” two cents.

Comment on What do we mean when we talk about pattern separation of stimuli anyways? by Michael Yassa Fri, 30 Aug 2013 03:12:55 +0000 I agree with Brad regarding the desire to think about input to the DG more carefully. As we mention in our review and in many conversations with Jim Knierim, understanding exactly how or whether the DG is decorrelating inputs cannot be done based on visual input or the stimuli themselves, but has to be done with consideration of the lateral and medial entorhinal inputs. Consistent also with Tim’s ideas I think that there is serial hierarchical decorrelation happening along the entire input stream with the conjunctive version of this decorrelation happening in the DG. This is also entirely consistent with Brad’s ideas that the DG is involved in the conjunctive encoding of what and where (and perhaps when), combining LEC and MEC inputs that way. Thinking about the type of information in addition to how the information is transformed is critically important in my opinion. We have done some work in this area recently with hi-res fMRI that is currently under review (given the exchanges on the website, I’m a little concerned we will receive “bipolar” reviews, as has been the experience for some here it seems).

Comment on Pattern separation: What’s the problem?! by John J. Sakon Fri, 30 Aug 2013 00:44:44 +0000 Glad to see all of this discussion and think Michael’s exhaustive review does a very good job structuring the pattern separation literature and formalizing the term.

Wanted to chime in from an outsider’s perspective in defense of Tim. I totally agree with Craig’s points in the other thread about the problems with ‘discrimination’. And I think ‘behavioral pattern separation’ makes sense intuitively to those that care enough to read pattern separation papers.

I can also tell you from my own outsider’s experience that use of the term ‘pattern separation’–while a bit unbridled–makes life easier on all of us. I did my PhD in an unrelated field and first heard of pattern separation 4 years ago. Partly the term itself inspired me to learn the concept and read a bunch more papers in the field (fun to see many of those authors in this thread!). Intuitively I came to understand ‘pattern separation’ as the cognitive ability to distinguish similar inputs, while ‘discrimination’ of dissimilar stimuli was handled by the brain differently. Yes it took dozens more papers for me to start questioning the blanket use of the term, but isn’t that true for any topic in any field?

So while I (and all of us serious scientist-types) agree with Adam’s general point to be careful about confusing the computational and behavioral definitions of pattern separation, I hardly think the potential confusion for the layman is hurting the field for those of us intent enough to be researching the topic. And as I’ve tried to indicate: I think the name has some useful cachet.

Comment on Pattern separation: What’s the problem?! by Craig Stark Thu, 29 Aug 2013 17:57:09 +0000 Jim wrote:

1) Formally, pattern separation is defined as the transformation of one input representation to an output representation, in which the output is less correlated than the input. One cannot directly test pattern separation as a function of a brain region without measuring the inputs to the brain region and its outputs.

Nobody can disagree with this and Adam’s points come down to the fact that many papers aren’t talking about this. So, when talking about behavior, we’re never going to have this and I believe I’ve always acknowledged this point. One take is that when working at a behavioral level, the term “pattern separation” should be verboten as, well, we can never hit the definition above. Anyone who does… off with their heads! 🙂

Here’s my problem. Can any of us ever use the term then? Do the neural papers – things that are showing overlap metrics via IEG expression or via recording actually hit this definition? I’d say they don’t. So, they’re not allowed to use the term as well. Anyone who does.. off with their heads!

At which point, the only time the term can be mentioned, outside of the inky shadows of back room conversations is in computational papers. To me, that would be a shame.

To me, the rise of the term “pattern separation” has been a great thing. It’s gotten human researchers to think a bit more about representations and about computations. It’s gotten them to pay attention to computational models. When was the last time that happened? (Sorry, but… remember all, I got my Ph.D. with Jay McClelland doing models.) Instead of thinking that the purpose of the hippocampus is to do “recollection”, people are starting to think about what it is about the hippocampus that lets it play a critical role in recollection, episodic memory, or whatever. Sure, there are growing pains and things get munged, but I’d rather have that than the total disconnect we’ve had until recently.

So, I hope we can come up with a way of talking about this that doesn’t push “pattern separation” into the 100% accurate but rarely really applicable corner.