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Science starts with observation, not experimentation. Honestly, if this was software, I'd consider this sort of approach as nothing short of pathetic. When I f

Science starts with observation, not experimentation. Honestly, if this was software, I'd consider this sort of approach as nothing short of pathetic. When I first reverse engineered firmware flashing software for mobile phones, experimentation was the absolute last thing I did - and all that experimentation could do was damage my phone, not another living creature. Instead I recorded observations of software operating under normal use (USB traces) and identified patterns in this. Only once I'd spent a long time determining patterns and built a model did I decide it was safe to perform some experimentation. To be fair, biological systems are much more complicated than computer systems written by other humans. However, observation should always come first! This study seems crude to me.

smhost 10y ago
> We next exploited cortical signals to decode the temporal structure of extensor and flexor hotspot activation. The spiking activity recorded from the left motor cortex displayed cyclic modulations that were phase-locked with right leg movements (Extended Data Fig. 4a). We developed a decoder that calculated the probability of foot-strike and foot-off events from this modulation to anticipate the activation of extensor and flexor hotspots associated with right leg movements (Extended Data Fig. 4b). Evaluations in two intact monkeys showed that the decoder accurately predicted these gait events in real time over extended periods of locomotion, including when initiating and terminating gait, and during rest. (Source: doi:10.1038/nature20118) Is that kind of what you mean?
- lostlogin 10y ago
  "Intact monkeys" is this a nice way of saying that they hadn't paralysed them yet?
  - smhost 10y ago
    Ya. They collected data from monkeys 1 and 2, then they injured monkeys 2 and 3. They collected data from monkeys 2 and 3, then they removed the spinal cord from all three.
scawf 10y ago
Do you think scientists are not recording normal use case ? Of course they use technology to observe and record normal and pathological "use". Do you think brain implants are made without using scanner, IRM...?
234dd57d2c8db 10y ago
You can't compare the two because one was created by humans and one was not. It's ridiculous to compare these two. Here's a more accurate scenario: You need to debug this software without a keyboard, mouse, monitor. The language is an assembly language written by aliens with no documentation that uses quantum states in protons to manage the machine. Oh by the way, it's encrypted and obfuscated into nothing but MOV instructions. And there's 100 billion MOV instructions. That's the kind of complexity we are talking about here. So get off your highhorse and let the experts who just made a paralyzed monkey walk do their jobs.
- fermuch 10y ago
  The phrasing is a bit harsh, but the example is a nice one. It's easy to forget how complex living creatures are.
- Benjamin_Dobell 10y ago
  Except they didn't exactly make a paralyzed monkey walk, did they? They simply paralyzed a monkey. There are parts of this study that seem quite legit (another poster referred to them above). However, the paralysis, surgery, and replay of data into the nervous system, just to be the first to "claim" they made a monkey walk was not one of them. I already mentioned software is very different to biology, my issue is with reckless experimentation that has caused a lot of harm to a creature and provides no real gain. What were they actually hoping to achieve with this part of the experiment? It's already well understood that we can interface with nervous system, this is nothing new. P.S. concern for the well being of other creatures isn't a particularly high horse. It's called empathy.
  - 234dd57d2c8db 10y ago
    It's not "reckless experimentation" for "no gain" at all. Here's a practical application for this research. Someone with a disease will eventually suffer from paralysis due to the degen. nature of the disease. Applying the technique from the research, we could record their body movements before they become paralyzed and then restore their ability to walk later. I think that's a pretty real gain. Just because it's in a fledgling stage of research doesn't mean it's worthless. Medical research is a much longer timeline than even complex software. You make incredibly small baby steps precisely because you don't have tools like a debugger, logic analyzer, etc, etc.
stinos 10y ago
> Science starts with observation, not experimentation. well, yes, but in a lot of neuroscience research, mainly the fundametal research, the initial observation stage led to the knowlegde that you first need controlled experimentation in order to perform any further valid/interesting observation at all
snowwrestler 10y ago
This is going to seem personally harsh--that's not my intention. But you're flatly wrong. Fundamentally, collecting observations is an active pursuit. An example: We didn't start to learn about electricity until we started messing with it. That's because there was very little to observe passively. Touching electric fish, rubbing amber to make static electricity, flying a kite into a thunderstorm--these sorts of actions produced the early observations that started us down the path toward the knowledge we have today. Your example was observing USB traces. In order to do that, you had to plug a well-understood sensor into a well-understood interface. You did something, and observed the results. You just think of it as passive observation because you're taking for granted the enormous amount of prior knowledge that made it possible.
- Benjamin_Dobell 10y ago
  I do agree with you here. My point is paralysing the monkey didn't help them collect data about how a monkey walks, quite the opposite. Reasonable observations would consist of using electrodes to monitor left leg movements vs right leg movements. Running vs walking, joint extension etc. Build a waveform generator and compare the generated waveforms vs real waveforms and iterate. (The scientists did actually do this.) Once you've got a fair degree of confidence then you can try apply your work. Paralysing a monkey just to replay captured data when we already know we can interface with the nervous system is totally unnecessary. Edit: It should really go without saying that when it does come time to apply your work you do everything within your power to avoid harming a non-consenting creature. Does applying the work even require paralysing a monkey? Can it be temporary? What about sedation and then interfacing with the nervous system whilst sedated?
adityab 10y ago
How do you suggest one should observe neural activity?
- lostlogin 10y ago
  EEG and MRI seem an obvious starting place, but use humans not monkeys, and this will give better data.
  - adityab 10y ago
    Computational Neuroscience student here. Research of this nature requires reading the electrical spike trains of small sets of neurons (often even individual cells). EEG will give you a measurement of the combined electric field of every single neuron that is active in the entire brain. You can use multiple electrodes and run machine learning algorithms to get a qualitative measure of a macroscopic chunk of brain activity. So, terrible spatial precision. MRI gives you anatomical information. fMRI gives an idea of blood flow in the brain (about millimeter precision which is also not good enough) which is a time-lagged (a few seconds) _response_ to sustained neural spiking in a region. Think of it like this: The brain is a computational organ where there is very little hardware-software separation. We're not going to be able to patch the software (say, to treat paralysis) without patching the hardware (say, with implants)
    - lostlogin 10y ago
      The point of my comment was that getting good testing is surely easier on humans than monkeys. Actually going in has to happen at some point - why not do this on humans that have volunteered? Cellular level investigations are obviously important but getting a wire in somewhere is not going to happen at a level this small. It will be image guided surely. X-ray would by my guess and hopefully MR but that obviously has its complexities as MR with additional wires isn't that straight forward. A decent MR DTI can help when you want to know where the fibres go, but as you say, the hardware/software division isn't quite so clear with live things.
      - 10y ago

smhost 10y ago

> We next exploited cortical signals to decode the temporal structure of extensor and flexor hotspot activation. The spiking activity recorded from the left motor cortex displayed cyclic modulations that were phase-locked with right leg movements (Extended Data Fig. 4a). We developed a decoder that calculated the probability of foot-strike and foot-off events from this modulation to anticipate the activation of extensor and flexor hotspots associated with right leg movements (Extended Data Fig. 4b). Evaluations in two intact monkeys showed that the decoder accurately predicted these gait events in real time over extended periods of locomotion, including when initiating and terminating gait, and during rest. (Source: doi:10.1038/nature20118) Is that kind of what you mean?

lostlogin 10y ago
"Intact monkeys" is this a nice way of saying that they hadn't paralysed them yet?
- smhost 10y ago
  Ya. They collected data from monkeys 1 and 2, then they injured monkeys 2 and 3. They collected data from monkeys 2 and 3, then they removed the spinal cord from all three.

scawf 10y ago

Do you think scientists are not recording normal use case ? Of course they use technology to observe and record normal and pathological "use". Do you think brain implants are made without using scanner, IRM...?

234dd57d2c8db 10y ago

You can't compare the two because one was created by humans and one was not. It's ridiculous to compare these two. Here's a more accurate scenario: You need to debug this software without a keyboard, mouse, monitor. The language is an assembly language written by aliens with no documentation that uses quantum states in protons to manage the machine. Oh by the way, it's encrypted and obfuscated into nothing but MOV instructions. And there's 100 billion MOV instructions. That's the kind of complexity we are talking about here. So get off your highhorse and let the experts who just made a paralyzed monkey walk do their jobs.

fermuch 10y ago
The phrasing is a bit harsh, but the example is a nice one. It's easy to forget how complex living creatures are.
Benjamin_Dobell 10y ago
Except they didn't exactly make a paralyzed monkey walk, did they? They simply paralyzed a monkey. There are parts of this study that seem quite legit (another poster referred to them above). However, the paralysis, surgery, and replay of data into the nervous system, just to be the first to "claim" they made a monkey walk was not one of them. I already mentioned software is very different to biology, my issue is with reckless experimentation that has caused a lot of harm to a creature and provides no real gain. What were they actually hoping to achieve with this part of the experiment? It's already well understood that we can interface with nervous system, this is nothing new. P.S. concern for the well being of other creatures isn't a particularly high horse. It's called empathy.
- 234dd57d2c8db 10y ago
  It's not "reckless experimentation" for "no gain" at all. Here's a practical application for this research. Someone with a disease will eventually suffer from paralysis due to the degen. nature of the disease. Applying the technique from the research, we could record their body movements before they become paralyzed and then restore their ability to walk later. I think that's a pretty real gain. Just because it's in a fledgling stage of research doesn't mean it's worthless. Medical research is a much longer timeline than even complex software. You make incredibly small baby steps precisely because you don't have tools like a debugger, logic analyzer, etc, etc.

stinos 10y ago

> Science starts with observation, not experimentation. well, yes, but in a lot of neuroscience research, mainly the fundametal research, the initial observation stage led to the knowlegde that you first need controlled experimentation in order to perform any further valid/interesting observation at all

snowwrestler 10y ago

This is going to seem personally harsh--that's not my intention. But you're flatly wrong. Fundamentally, collecting observations is an active pursuit. An example: We didn't start to learn about electricity until we started messing with it. That's because there was very little to observe passively. Touching electric fish, rubbing amber to make static electricity, flying a kite into a thunderstorm--these sorts of actions produced the early observations that started us down the path toward the knowledge we have today. Your example was observing USB traces. In order to do that, you had to plug a well-understood sensor into a well-understood interface. You did something, and observed the results. You just think of it as passive observation because you're taking for granted the enormous amount of prior knowledge that made it possible.

Benjamin_Dobell 10y ago
I do agree with you here. My point is paralysing the monkey didn't help them collect data about how a monkey walks, quite the opposite. Reasonable observations would consist of using electrodes to monitor left leg movements vs right leg movements. Running vs walking, joint extension etc. Build a waveform generator and compare the generated waveforms vs real waveforms and iterate. (The scientists did actually do this.) Once you've got a fair degree of confidence then you can try apply your work. Paralysing a monkey just to replay captured data when we already know we can interface with the nervous system is totally unnecessary. Edit: It should really go without saying that when it does come time to apply your work you do everything within your power to avoid harming a non-consenting creature. Does applying the work even require paralysing a monkey? Can it be temporary? What about sedation and then interfacing with the nervous system whilst sedated?

adityab 10y ago

How do you suggest one should observe neural activity?

lostlogin 10y ago
EEG and MRI seem an obvious starting place, but use humans not monkeys, and this will give better data.
- adityab 10y ago
  Computational Neuroscience student here. Research of this nature requires reading the electrical spike trains of small sets of neurons (often even individual cells). EEG will give you a measurement of the combined electric field of every single neuron that is active in the entire brain. You can use multiple electrodes and run machine learning algorithms to get a qualitative measure of a macroscopic chunk of brain activity. So, terrible spatial precision. MRI gives you anatomical information. fMRI gives an idea of blood flow in the brain (about millimeter precision which is also not good enough) which is a time-lagged (a few seconds) _response_ to sustained neural spiking in a region. Think of it like this: The brain is a computational organ where there is very little hardware-software separation. We're not going to be able to patch the software (say, to treat paralysis) without patching the hardware (say, with implants)
  - lostlogin 10y ago
    The point of my comment was that getting good testing is surely easier on humans than monkeys. Actually going in has to happen at some point - why not do this on humans that have volunteered? Cellular level investigations are obviously important but getting a wire in somewhere is not going to happen at a level this small. It will be image guided surely. X-ray would by my guess and hopefully MR but that obviously has its complexities as MR with additional wires isn't that straight forward. A decent MR DTI can help when you want to know where the fibres go, but as you say, the hardware/software division isn't quite so clear with live things.
    - 10y ago