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Kathleen Rockland on neocortex and cortical anatomy

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Season 2011
Season 2011
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Is the neocortex really uniform , and do feedforward and feedback connections mean what we think they mean? Kathleen Rockland challenges foundational assumptions about cortical organization with evidence that structure and function are more discrepant than textbooks suggest. Subscribe for more from the Convergent Science Network podcast series. Kathleen Rockland is a neuroanatomist who has spent her career examining cortical connectivity at a level of detail that most theorists and imagers never encounter. In this interview, she delivers a series of provocative challenges to standard assumptions about how the neocortex is organized. Her first point is counterintuitive: the most striking property of cortical axons is not their specificity but their divergence. When you trace individual axons and examine their collateralization, the word that comes to mind is distributed , connections fan out broadly before any question of specificity arises. Rockland then dismantles the textbook story of ocular dominance columns. The functional columns are unambiguously about 500 microns in diameter, but the anatomical inputs that supposedly create them, thalamocortical axons from the LGN, come in at wildly different scales: parvocellular arbors at 250 microns, magnocellular clusters larger with multiple foci, layer 4A inputs at 100 microns, and layer 1 projections that are highly divergent. Some operation within intrinsic cortical circuitry must be converging these mismatched inputs into the 500-micron functional unit. This means that thalamocortical connections are not the basis of ocular dominance columns in any simple sense , the cortex itself is doing something essential to create the functional organization we observe. The conversation turns to feedforward and feedback pathways, which Rockland argues carry misleading temporal assumptions. She proposes reframing these as layer-4-biased connections and layer-1-biased connections, respectively , a description that captures the anatomical reality without implying a sequential relay. In rodents, the laminar scheme breaks down substantially, and even in primates there are abundant exceptions. Rockland also notes that the supposed unimodality of primary sensory areas is threshold-dependent: lower your detection threshold and cross-modal inputs appear even in monkey V1 and V2. Her overarching message is that structure-function correlation, long treated as a guiding principle, is more often the exception than the rule. The brain works, but not in the way our simplified models suggest.

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Both the triumphs of humanity and its most evil deeds have resulted from collaboration. In a time where humanity is required to aspire to the former and minimize the latter, the question arises of how collaboration arises and why it fails. Surprisingly, this phenomenon, so central to who we are, is not well understood. Hence, a collaborative effort is required to understand collaboration in its full biological, psychological, sociological, cultural, and economic complexity and to translate this understanding into operational impact. This series of podcasts is one step toward achieving these complementary goals. The Collaboration Podcast presents interviews with people who are central orchestrators of collaboration in various domains including business, government, science, art, health, sustainability, and the military. The discussions were conducted by Prof. Dr. Paul F.M.J. Verschure and members of the Program Advisory Committee of the Ernst Strungmann Forum on Collaboration (https://www.esforum.de/forums/ESF32_Collaboration.html) during 2021 and had the goal to sketch a map of opportunities, challenges, and obstacles in human collaboration. The forum took place in May 2022, and now we would like to share this series of interviews with a broader audience. The full report of the Forum will be published in 2023 by MIT Press. The podcast was produced by the Convergent Science Network (https://www.convergentsciencenetwork.org/). Context: The stability of social systems depends critically on realizing sustainable methods of “collaboration,” yet how and by which means collaboration is achieved is not clearly understood; neither are the conditions or processes that lead to its breakdown or failure. Collaboration can be understood as cooperation between agents toward mutually constructed goals. Part of the reason for our lack of understanding is that the phenomenon of collaboration is, by nature, a highly multidisciplinary problem, and effective research into its complexities has been difficult to achieve across the broad range of scientific and technical disciplines involved. The need for a fundamental understanding of collaboration, however, has become increasingly important. Not only does humankind demand answers as it attempts to address critical challenges at multiple scales (e.g., climate change, migration, enhanced automation, social and economic inequality), but ever-increasing technological and economic means of interconnecting people and societies are disrupting long-established, familiar patterns of how we interact. Radical technological changes that are ongoing have the potential to reshape collaboration in ways that are currently hard to predict or influence (e.g., by altering configurations in interaction, information creation, and modes of communication). On one hand, such changes could disrupt hitherto stable forms of collaboration by affecting critical communication channels and traditional roles, as can be observed in the rapidly changing patterns in governance, commerce, and social interaction. Conversely, technology could lead to the emergence of novel, successful forms of collaboration that deviate from traditional “hierarchical” architectures. Evidence of this can be seen in areas as diverse as highly automated manufacturing plants, the open science movement, collaborative software repositories, user-centered services, and the sharing of economy-based modes of organization. Without a fundamental understanding of the mechanisms, processes, and boundary conditions of collaboration, it is not possible to evaluate or predict which of these possible scenarios are sustainable or even plausible. The Forum “How Collaboration Arises and Why it Fails” (May 8–13, 2022, Location: Frankfurt am Main, Germany) Chairs: Andreas Roepstorff and Paul Verschure Program Advisory Committee: Jenna Bednar, Julia R. Lupp, Bhavani R. Rao , Andreas Roepstorff, Ferdinand von Siemens, and Paul Verschure

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  • fast_forward00:00:00 - So I'm here with, this is Paul Vachure with Kathy Roepland at the Catherly Center
  • fast_forward00:00:05 - for Theoretical Physics.
  • fast_forward00:00:07 - We're both attending a workshop on network architecture and the brain.
  • fast_forward00:00:11 - And Kathy, you gave us a presentation yesterday where you really gave us quite
  • fast_forward00:00:17 - a broad overview of the anatomy of mainly cerebral cortex.
  • fast_forward00:00:21 - Yes. So, what do you think are the key properties of a neocortex that we should
  • fast_forward00:00:29 - be aware of? Of the neocortex?
  • fast_forward00:00:37 - Well, let me start with what may seem backwards and say I think the distributed property.
  • fast_forward00:00:47 - Most people are not going to say this first thing. But if you look at these
  • fast_forward00:00:52 - axons, and you look at the divergence, and you look at the collateralization.
  • fast_forward00:00:57 - The first word, English word, that comes to your mind is distributed or divergent.
  • fast_forward00:01:04 - Now we can proceed a little bit more. That immediately gets you into questions
  • fast_forward00:01:09 - of probably random or specific, which we can come back to.
  • fast_forward00:01:15 - I'm not saying random, I'm just saying simple fact of distributed.
  • fast_forward00:01:21 - And so that's one thing we can come back to. Probably what most people would
  • fast_forward00:01:26 - then talk about the cortex is because it's been promoted and promoted and promoted,
  • fast_forward00:01:34 - a uniform organization,
  • fast_forward00:01:36 - this is what we were talking about at lunch.
  • fast_forward00:01:38 - But that really, if you look closely at the anatomy, that's not the first thing that comes to mind.
  • fast_forward00:01:45 - I could show you pictures later. We can develop that theme also.
  • fast_forward00:01:50 - Having said that, I would then introduce the idea that, which many people are
  • fast_forward00:01:57 - saying, that the anatomy and the function is a little bit discrepant.
  • fast_forward00:02:02 - We've been, again, trained to say structure-function correlation.
  • fast_forward00:02:08 - But now it's very clear that there can be functional aspects and structural
  • fast_forward00:02:12 - aspects, and sometimes there's an apparent discrepancy.
  • fast_forward00:02:16 - Cortex, of course, can deal with it, but for us it looks... Can you give an
  • fast_forward00:02:20 - example of discrepancy? Yeah, I think, and we might have talked about this yesterday also.
  • fast_forward00:02:25 - One of my favorite examples, and you can pick this apart, please,
  • fast_forward00:02:30 - is ocular dominance columns in the monkey.
  • fast_forward00:02:34 - So you are shown ocular dominance columns with beautiful 2DG,
  • fast_forward00:02:40 - so an eye is blocked and you see the 2DG pattern more or less through the layers.
  • fast_forward00:02:47 - It's very convincing. It's very real. Then you are told what is the truth,
  • fast_forward00:02:53 - that the basis of this is thalamocortical connectivity.
  • fast_forward00:02:59 - Now, there are actually several things to say about that. One is,
  • fast_forward00:03:03 - if you look at the scale of the anatomy and the functional column,
  • fast_forward00:03:09 - there's an immediate mismatch.
  • fast_forward00:03:11 - So in layer 4C, the main layer, parvosellular axons are smaller than 500.
  • fast_forward00:03:20 - I should say the ocular functional columns are about 500 microns in diameter.
  • fast_forward00:03:26 - But the parvosellular LGN is smaller, 250.
  • fast_forward00:03:31 - Magnocellular is larger, with two or three clusters.
  • fast_forward00:03:35 - Then 4A, you have another population of thalamocortical axons.
  • fast_forward00:03:40 - It's very small, 100 microns, center to center.
  • fast_forward00:03:45 - Sometimes they're collaterals in layer 6. These tend to be smaller.
  • fast_forward00:03:49 - The cytochrome oxidase population is the axons are less than,
  • fast_forward00:03:54 - equal or less than 100 microns.
  • fast_forward00:03:57 - And in layer 1, whatever goes up there from the LGM is very divergent.
  • fast_forward00:04:02 - So I was puzzled by this for a long time, and my own explanation is there must
  • fast_forward00:04:08 - be some operation, something, some operation, which is making those axons converge,
  • fast_forward00:04:14 - and the key word here would be maybe something operation, and converge in a 500 micron space.
  • fast_forward00:04:20 - And the two candidates would be something molecular.
  • fast_forward00:04:26 - Going back to development presumably, maybe extracellular matrix,
  • fast_forward00:04:30 - and activity-related, or and or both.
  • fast_forward00:04:33 - Okay, so here, let me summarize. The functional column is unambiguously bicarbonate
  • fast_forward00:04:39 - microns, but the anatomical basis of this, the primary anatomical basis,
  • fast_forward00:04:44 - is all, I'll use the same term probably several times, all around the block.
  • fast_forward00:04:49 - Now, of course, the reconciliation, we think, would be from the intrinsic processing, But that gets you in.
  • fast_forward00:04:55 - It's not the same thing as saying thalamocortical connections are the basis
  • fast_forward00:04:59 - of ocular dominance columns.
  • fast_forward00:05:01 - It means that the cortex is doing, the intrinsic cortex is doing something on those connections.
  • fast_forward00:05:08 - But how do you then define this functional scale of organization of 500 micron?
  • fast_forward00:05:14 - What you would see, well, so my first response is operationally that you can link.
  • fast_forward00:05:20 - I think if you have a functional marker like 2-D-alcyclicose or CFOS,
  • fast_forward00:05:25 - and you can link it to a behavior, you will tend to see a columnar,
  • fast_forward00:05:30 - often a columnar organization of this amount.
  • fast_forward00:05:35 - Does that, does that want to go a little bit further? No, go ahead, go ahead.
  • fast_forward00:05:38 - But having said that, there is some beautiful work, and I'm sorry I forget the
  • fast_forward00:05:43 - authors here, but it was within the last five years on the CFOS of...
  • fast_forward00:05:49 - Might have been Japanese group Yamamori where
  • fast_forward00:05:53 - they were looking at different
  • fast_forward00:05:56 - conditions of ocular deprivation in
  • fast_forward00:06:00 - the monkey in CCOS which is a better resolution than the 2DG and they would
  • fast_forward00:06:09 - see they were able to see several laminar patterns depending on the time interval
  • fast_forward00:06:14 - and what they had actually done with the ocular dominant.
  • fast_forward00:06:18 - So even there, there is a suggestion that when you're looking at average techniques.
  • fast_forward00:06:26 - It's telling you part of reality, but not the whole.
  • fast_forward00:06:30 - Okay, so one bottom line of this is that structural and functional organization
  • fast_forward00:06:36 - does not necessarily matter.
  • fast_forward00:06:39 - Not to the investigative view. So it works in biology, but not in the way we
  • fast_forward00:06:46 - might think. There's no simple mapping between the two. Often not.
  • fast_forward00:06:49 - In fact, when it occurs, it's almost the exception.
  • fast_forward00:06:53 - And one exception would be, for example, corticospinal tract,
  • fast_forward00:06:57 - where you have the difference of primate with the fine pincer movement versus
  • fast_forward00:07:02 - the carnivores that cup. And there is an anatomical basis.
  • fast_forward00:07:06 - Or even the development of the corticospinal tract, so babies can't walk until
  • fast_forward00:07:11 - the corticospinal tract does something, myelination, maybe other things.
  • fast_forward00:07:14 - But I've come to think it's almost the exception.
  • fast_forward00:07:19 - Okay. But now in your presentation, you also went a bit further than that, right?
  • fast_forward00:07:22 - Because you also pointed out that the sort of standard notions of feed forward
  • fast_forward00:07:28 - and feed back that people have been using to describe the structure of the cortex
  • fast_forward00:07:32 - might not be that clear-cut either.
  • fast_forward00:07:35 - Absolutely. And I think in several ways.
  • fast_forward00:07:41 - One, even if you take the schematic, the strong view with layers and so on,
  • fast_forward00:07:47 - There are many exceptions, really abundant exceptions.
  • fast_forward00:07:51 - And when you go to the rodent, it's been well known for years that the laminar-based
  • fast_forward00:07:57 - scheme breaks down in a big way.
  • fast_forward00:08:00 - You have a layer one is favored maybe by what could be feedback.
  • fast_forward00:08:06 - Layer four is favored, but there's a tremendous blurring.
  • fast_forward00:08:11 - But even within primate, you have a lot of exceptions. But what are the rules,
  • fast_forward00:08:16 - really, on which we have these exceptions?
  • fast_forward00:08:20 - What do you mean by that? Well, as you say, you have many exceptions in rodent
  • fast_forward00:08:24 - and also in monkey, but then there's a rule to which you have an exception,
  • fast_forward00:08:28 - right? So what's the rule for it?
  • fast_forward00:08:30 - All right. Well, the old rule, which has some basis, in fact,
  • fast_forward00:08:35 - in static anatomical fact, is that… Okay, feed forward.
  • fast_forward00:08:43 - See, it's really based on a relay view of the brain, and I don't think that's very useful.
  • fast_forward00:08:49 - But if you accept that relay view, the visual information goes to the eye,
  • fast_forward00:08:54 - goes to the LGN, goes to V1, and so on.
  • fast_forward00:08:57 - Then, and of course, V1 goes to LGN, but also other things go to LGN.
  • fast_forward00:09:03 - So none of these are pairwise. Absolutely none.
  • fast_forward00:09:07 - When you get to V1, and you say, okay, let's start the relay from there. and if you do V1, V2, V3,
  • fast_forward00:09:15 - let's just put in MT, extra striate, V4, infratemporal cortex,
  • fast_forward00:09:19 - there is, you can plausibly say layer 3 goes to layer 4, an input layer, in your feedforward.
  • fast_forward00:09:32 - And the feedback is actually usually two layers, layer 6 and layer 2,
  • fast_forward00:09:38 - feeding back to layer 1 and sometimes layer 6.
  • fast_forward00:09:42 - But there is a dissociation, one can present a dissociation of a Layer 4-based
  • fast_forward00:09:50 - feed-forward and a Layer 1-based feedback.
  • fast_forward00:09:54 - And there also is, this was the data, these were the data I was showing yesterday,
  • fast_forward00:09:58 - a dissociation in spatial organization.
  • fast_forward00:10:01 - Feed-forward tends to have smaller arbors, sometimes multiple,
  • fast_forward00:10:05 - feedback divergent in Layer 1.
  • fast_forward00:10:08 - But I would still, I suggested yesterday and would still like to suggest that
  • fast_forward00:10:16 - you can rephrase this in terms of a Layer 1 organization or a Layer 1 biased
  • fast_forward00:10:22 - connection and a Layer 4 biased connection.
  • fast_forward00:10:26 - There's no real need to say feed forward and feed back in that.
  • fast_forward00:10:30 - And it has a very bad assumption of saying, well, something happened,
  • fast_forward00:10:35 - and then there was a feedback.
  • fast_forward00:10:38 - But we don't know when the film started.
  • fast_forward00:10:42 - So there is a strong assumption in the terminology of this temporal or relay
  • fast_forward00:10:49 - pattern, which I think is not, it can be useful to an extent,
  • fast_forward00:10:52 - but it cannot be the whole truth.
  • fast_forward00:10:55 - Right. Okay. Okay, but then another issue then becomes this so-called uniformity of cortex, right?
  • fast_forward00:11:03 - So, for instance, you would say, well, we have a layered structure.
  • fast_forward00:11:06 - And pseudo-architectonically, it sort of roughly remains the same if we sort
  • fast_forward00:11:12 - of go from the front to the back, right?
  • fast_forward00:11:15 - And also there would then be this idea that maybe in terms of their functional
  • fast_forward00:11:20 - organization, things will change in the sort of occipital areas and parietals,
  • fast_forward00:11:25 - more sensory, and if we go more frontal, we go more motor.
  • fast_forward00:11:28 - Is that then at least a pattern we can still sort of adhere to?
  • fast_forward00:11:33 - Yes, by all means. But of course, I'm going to say but.
  • fast_forward00:11:37 - And you have to keep in mind the threshold problem, which is glaringly obvious in fMRI.
  • fast_forward00:11:46 - So if you set your, if I understand correctly, if you set your threshold low
  • fast_forward00:11:50 - enough, you're going to see lots of stuff.
  • fast_forward00:11:53 - And it's apparent...
  • fast_forward00:11:56 - I think, well, V1, your sensory areas in the adult, in the primate,
  • fast_forward00:12:04 - probably do function strongly unimodal. But there are these cross-modal connections.
  • fast_forward00:12:11 - Even in monkey, I'm going to say it's in the peripheral visual field.
  • fast_forward00:12:19 - Maybe a little bit less in the fovea. So this, again, would substantiate the threshold phenomenon.
  • fast_forward00:12:26 - But in monkey V2, to some extent V1, you have, in V2 it's quite respectable.
  • fast_forward00:12:33 - You have auditory input, you have sensory input, in the rodent you have.

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