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Connectome-adjacent neuroscientist here. Definitely not a dead end! But also definitely not the whole picture. One of the main open questions in neuroscience r

Connectome-adjacent neuroscientist here. Definitely not a dead end! But also definitely not the whole picture. One of the main open questions in neuroscience right now is how network structure, dynamics, and function are related in the brain. Connectomes provide tremendous insight into structure, but as mentioned this does not generically solve either the dynamics or function problem. For example, for many of these neurons we don't have a good understanding of their input-output relationship, and the nature of this relationship can strongly affect the dynamics that emerge in a highly connected network. Individual variability across connectomes, and how connectomes change over development are also a significant issue, but at least for the fly it's thought that many of the basic structures are pretty conserved across adult animals, even if many of the details could differ. Modulo these caveats, knowing the physical network structure of the brain does still impose huge constraints on what kinds of models we should be using for gaining insight into dynamics and function. For example, there are well known areas (the "mushroom bodies") with specific feed-forward connectivity patterns that are very different from a random recurrent network. Further, there are at least some areas in the fly brain where we think there are indeed quite clean structure-function relationships, e.g. in the central complex of the fly brain, which contains a physical ring of neurons and is thought to support a "bump" of activity that acts as a sort of compass that helps flies navigate via a ring-attractor-like dynamical system. Thus, even though it has many missing pieces, a wiring diagram like this can be tremendously useful for generating hypotheses to guide more targeted experiments and theoretical studies.

Animats 2y ago
How's Open Worm coming along? The connectome of C. Elegans has been known for years, and Open Worm tries to simulate it. [1] Not with enormous success. [1] https://openworm.org/assets/OpenWormPoster_Celegans_Glasgow_2023.pdf https://openworm.org/assets/OpenWormPoster_Celegans_Glasgow_...
- xandrius 2y ago
  Like everything in science: we don't know until we know. No need to treat research like a business.
  - cafebeen 2y ago
    Budgets are finite, and most science funding involves some decision making about how to allocate resources.
    - bboygravity 2y ago
      And you can't know where to allocate resources best until after the science is done (unless a field/group is known to scam).
    - xandrius 2y ago
      Although for what we know now, we definitely can't understand the territory without a map.
    - consf 2y ago
      [dead]
    - mr_toad 2y ago
      It’s a non-profit volunteer run project. People spend more money on stamp collections.
  - beefnugs 2y ago
    You know you would have thought all the years and years of "donations" to "cancer research" there would be constant news stories about how we accidentally cured a bunch of ancillary medical problems, and wow its all free to everyone because it was from donations! Never heard a single story like this
    - ben_w 2y ago
      Human Genome Project and everything derived from it. IIRC, that was originally proposed as a cancer research project: "A Turning Point in Cancer Research: Sequencing the Human Genome" - https://www.science.org/doi/10.1126/science.3945817 https://www.science.org/doi/10.1126/science.3945817 Even without that I'm not sure why you think that's a good point — it's very easy to find serendipitous examples in medicine in general, e.g. viragra which was initially a heart treatment, or even thalidomide whose anti-cancer uses were suggested by the very birth defects that made it infamous. Specifically cancer research finding other things by accident: "Cancer researchers accidentally discover ‘cure’ for baldness, gray hair" - https://technology.inquirer.net/62453/cancer-researchers-accidentally-discover-cure-baldness-gray-hair https://technology.inquirer.net/62453/cancer-researchers-acc... "Cancer Researchers Accidentally Discover New Nylon Process" - https://www.popularmechanics.com/science/health/a8135/cancer-researchers-accidentally-discover-new-nylon-process-13033053/ https://www.popularmechanics.com/science/health/a8135/cancer...
SubiculumCode 2y ago
Very Nice. --from a Connectome-Centric neuroimager :) One technique that I am pursuing right now is information decomposition of timeseries to separate the mutual information of two timeseries into redundant and synergistic informational atoms (synnergystic here means the degree to which knowing both timeseries gives you more information than the individual parts give (more than sum of parts). The big limitation of the method is the geometric explosion in complexity of the decomposition as the number of time series grow, with most analyses being limited to two or three times series at a time. However, the scale of the data on which it is applied is not requisite, meaning the approach can equally be used on the mutual information between two regions of interest in rsfMRI , or two spiking timeseries from individual neurons. https://en.wikipedia.org/wiki/Partial_information_decomposition https://en.wikipedia.org/wiki/Partial_information_decomposit...
taneq 2y ago
Thanks for your insight! How repeatable are these structures between individual animals? Are they very similar or is it more like “here’s a feed forward kinda bit, here’s a toroidal bit, and over here it’s just a mess”?
- j6m8 2y ago
  preprint coming out soon about this specifically :) in the meantime, here's a simple tool paper we wrote explaining how you can treat this like a cool graph database challenge [1] and a preprint showing how you could approach that question when your number of samples per animal is close to N=1 [2]. basically..... it's hard! but also.... it's cool! [1]: https://www.nature.com/articles/s41598-021-91025-5 https://www.nature.com/articles/s41598-021-91025-5 [2]: https://www.biorxiv.org/content/10.1101/2023.10.16.562590v1.full.pdf https://www.biorxiv.org/content/10.1101/2023.10.16.562590v1....
consf 2y ago
[dead]

Animats 2y ago

How's Open Worm coming along? The connectome of C. Elegans has been known for years, and Open Worm tries to simulate it. [1] Not with enormous success. [1] https://openworm.org/assets/OpenWormPoster_Celegans_Glasgow_2023.pdf https://openworm.org/assets/OpenWormPoster_Celegans_Glasgow_...

xandrius 2y ago
Like everything in science: we don't know until we know. No need to treat research like a business.
- cafebeen 2y ago
  Budgets are finite, and most science funding involves some decision making about how to allocate resources.
  - bboygravity 2y ago
    And you can't know where to allocate resources best until after the science is done (unless a field/group is known to scam).
  - xandrius 2y ago
    Although for what we know now, we definitely can't understand the territory without a map.
  - consf 2y ago
    [dead]
  - mr_toad 2y ago
    It’s a non-profit volunteer run project. People spend more money on stamp collections.
- beefnugs 2y ago
  You know you would have thought all the years and years of "donations" to "cancer research" there would be constant news stories about how we accidentally cured a bunch of ancillary medical problems, and wow its all free to everyone because it was from donations! Never heard a single story like this
  - ben_w 2y ago
    Human Genome Project and everything derived from it. IIRC, that was originally proposed as a cancer research project: "A Turning Point in Cancer Research: Sequencing the Human Genome" - https://www.science.org/doi/10.1126/science.3945817 https://www.science.org/doi/10.1126/science.3945817 Even without that I'm not sure why you think that's a good point — it's very easy to find serendipitous examples in medicine in general, e.g. viragra which was initially a heart treatment, or even thalidomide whose anti-cancer uses were suggested by the very birth defects that made it infamous. Specifically cancer research finding other things by accident: "Cancer researchers accidentally discover ‘cure’ for baldness, gray hair" - https://technology.inquirer.net/62453/cancer-researchers-accidentally-discover-cure-baldness-gray-hair https://technology.inquirer.net/62453/cancer-researchers-acc... "Cancer Researchers Accidentally Discover New Nylon Process" - https://www.popularmechanics.com/science/health/a8135/cancer-researchers-accidentally-discover-new-nylon-process-13033053/ https://www.popularmechanics.com/science/health/a8135/cancer...

SubiculumCode 2y ago

Very Nice. --from a Connectome-Centric neuroimager :) One technique that I am pursuing right now is information decomposition of timeseries to separate the mutual information of two timeseries into redundant and synergistic informational atoms (synnergystic here means the degree to which knowing both timeseries gives you more information than the individual parts give (more than sum of parts). The big limitation of the method is the geometric explosion in complexity of the decomposition as the number of time series grow, with most analyses being limited to two or three times series at a time. However, the scale of the data on which it is applied is not requisite, meaning the approach can equally be used on the mutual information between two regions of interest in rsfMRI , or two spiking timeseries from individual neurons. https://en.wikipedia.org/wiki/Partial_information_decomposition https://en.wikipedia.org/wiki/Partial_information_decomposit...

taneq 2y ago

Thanks for your insight! How repeatable are these structures between individual animals? Are they very similar or is it more like “here’s a feed forward kinda bit, here’s a toroidal bit, and over here it’s just a mess”?

j6m8 2y ago
preprint coming out soon about this specifically :) in the meantime, here's a simple tool paper we wrote explaining how you can treat this like a cool graph database challenge [1] and a preprint showing how you could approach that question when your number of samples per animal is close to N=1 [2]. basically..... it's hard! but also.... it's cool! [1]: https://www.nature.com/articles/s41598-021-91025-5 https://www.nature.com/articles/s41598-021-91025-5 [2]: https://www.biorxiv.org/content/10.1101/2023.10.16.562590v1.full.pdf https://www.biorxiv.org/content/10.1101/2023.10.16.562590v1....

consf 2y ago

[dead]