[Comp-neuro] Hilbert's questions

Randall O'Reilly randy.oreilly at colorado.edu
Tue Aug 12 19:51:25 CEST 2008


I wouldn't expect to convince someone like you, but perhaps if you  
actually read the papers on this particular topic, you would see that  
the models can account for a huge range of biological and behavioral  
data, and critically make predictions that are being tested and  
validated.  Not all ideas are wrong.  Just the wrong ones.

- Randy

On Aug 12, 2008, at 11:44 AM, james bower wrote:

> Wonderful what can be done with selective attention to detail,  
> overarching principles, and preconceived notions.
>
> "the hippocampus is essentially a solved problem" speaks for itself.
>
> so where the 'laws' of planetary motion, for about 1700 years.
>
> There is no doubt, that course (what it does) to fine (how it does  
> it) science is very efficient -- problem is, the course tends to  
> impose on the fine.
>
> Aspects of cognitive neuroscience may be the best examples, perhaps  
> in the history of science, of the danger of overarching ideas, in  
> the presence of non-structural models.
>
>
> Jim Bower
>
>
>
> On Aug 12, 2008, at 12:19 PM, Randall O'Reilly wrote:
>
>> There has been a remarkable absence of consideration for the  
>> functional level of the brain: i.e., the huge field of cognitive  
>> neuroscience, in this discussion and in the field of computational  
>> neuroscience in general.  There is no way you are going to figure  
>> out something as complex as the brain using a purely bottom-up  
>> strategy.  If you look at the work in computational *cognitive*  
>> neuroscience, where the behavioral level of analysis is taken  
>> seriously, the picture is much less bleak than the assessments  
>> provided here.  There are many models that relate the biological  
>> properties of neurons and brain areas to cognitive functions  
>> associated with those brain areas, and do a very good job of  
>> capturing a large proportion of the variance of both levels.
>>
>> For example, the hippocampus is essentially a "solved problem" in  
>> terms of the general framework for how its biological properties  
>> enable its well established role in memory.  Recent work by  
>> Tonagawa's group and several others have verified the predictions  
>> from a number of generally convergent computational models,  
>> regarding the specific roles of areas CA3, DG, CA1, etc.  By  
>> capturing the most global, high-level properties of the system  
>> first, across both behavior and biology, these models provide a  
>> framework within which more detailed questions and models can be  
>> developed.
>>
>> In almost every domain, a hierarchical coarse-to-fine strategy is  
>> the most efficient way to understand something.  First you figure  
>> out the most basic properties of the system, and then you fill in  
>> the details.  Some would argue that this is not possible in the  
>> brain, but I think the existing work already refutes that  
>> argument.  People who remain fixated on individual neurons and  
>> synapses may not appreciate this, and regard the system as a huge  
>> unsolved puzzle, but this is just because they are so zoomed in on  
>> the details that they are missing the big picture.  The big picture  
>> is filling in quite rapidly.  There are similarly successful models  
>> for prefrontal cortex, basal ganglia, and sensory neocortex, etc.
>>
>> Taken together these models strongly suggest that, to understand  
>> how the system actually functions, you don't need to simulate every  
>> last detail of a neuron, nor its connectivity.  Certain details are  
>> rather important (e.g., inhibition in the hippocampus is critical  
>> for establishing a sparse distributed representation, which  
>> minimizes interference and enables episodic memory, place cells,  
>> etc), but in general a fairly simple "integrate and fire" model of  
>> the neuron is sufficient to capture a large portion of the  
>> functional variance of what the brain actually does.
>>
>> Of course, I can't "prove" any of these assertions to the  
>> satisfaction of all skeptics, and I'm rather an optimist overall,  
>> but I think this field is definitely missing out on the big  
>> picture.  Certainly there is a huge amount still unknown, but if  
>> you squint your eyes just right, I think the picture is filling in  
>> quite nicely..
>>
>> - Randy
>>
>> On Aug 12, 2008, at 9:47 AM, james bower wrote:
>>
>>> I would say for sure that individual neurons are communicating --  
>>> just that communication is not dependent on any individual neuron  
>>> (in mammals), nor can one understand what they are communicating  
>>> independent of the population - a nice enigma.
>>>
>>> With respect to wiring - 'we' believe that nervous systems  
>>> represent what they know in their wiring -- 'we' also believe that  
>>> the modification of wiring takes place at the level of individual  
>>> neurons (and even synapses).  So for didactic purposes:
>>>
>>>
>>> 1) does the function of an individual brain depend on the detailed  
>>> wiring of that brain (likely)
>>> 2) can we therefore understand how brains function in general, by  
>>> working on multiple individuals let alone multiple species
>>> 3) in other words, what level of wiring specification do we need?
>>>
>>> and do we have the patience?
>>>
>>> Speaking of grubby, now probably mostly lost in history, the first  
>>> ''realistic network" modeling effort I ever saw presented was of  
>>> the sea slug tritonia, by an engineer (MIT) turned serious  
>>> experimentalist, Peter Getting - Neuroscience 1981, I think.
>>>
>>> Peter Getting had originally taken a faculty position at Stanford,  
>>> and, on the assumption that wiring was everything, set about  
>>> trying to understand the connections between the few (I think 6)  
>>> types of motoneurons that control the swimming (if you want to  
>>> call it that) of Tritonia.  Problem was that after his 6 year  
>>> junior faculty appointment, he had only completed characterizing 3  
>>> of the 6 (as I remember) sets of connections.  This was not deemed  
>>> reasonable progress, he was denied tenure and ended up taking a  
>>> position in Iowa, where he steadfastly continued to complete the  
>>> circuitry.  He did, and presented the results at the neuroscience  
>>> meeting -- and I remember being astounded.  Peter would have  
>>> actually been a major part of the first course in woods hole, had  
>>> he not had a massive stroke while running (which he did many miles  
>>> per day), ending up incapacitated.
>>>
>>> However, for sure, we now know from invertebrate systems that the  
>>> individual connections of individual neurons within an individual  
>>> matter --
>>>
>>> So -- if one believes in the importance of wiring -- shouldn't we  
>>> all be working in invertebrate preparations?
>>>
>>> Not an entirely rhetorical question -- it is clear from the  
>>> history of science in general and physics in particular that  
>>> picking the right problem is a key to progress.  Thus, Newton  
>>> 'discovered' the inverse square law by examining the (nearly)  
>>> circular orbit of the moon around the earth, for which he also had  
>>> much better distance data, rather than looking at the sexier  
>>> elliptical movements of the planets around the sun.
>>>
>>> Maybe we should give up on cerebral cortex for several hundred  
>>> years and all study tritonia instead.
>>>
>>>
>>> Jim
>>>
>>>
>>>
>>> On Aug 12, 2008, at 10:08 AM, Bill Lytton wrote:
>>>
>>>>
>>>>> grandest level it seems to me there is only one question: "What  
>>>>> is each neuron communicating,
>>>>> and how is the message encoded."
>>>>
>>>> I thought it was noted in recent discourse that the answer is  
>>>> nothing and not? -- ie
>>>> populations are needed.
>>>>
>>>>> That said, it could be an interesting exercise to come up with a  
>>>>> list of the current Top Ten
>>>>> Topics attracting the attention of
>>>>
>>>> Personally I would echo Martin and Douglas in their many papers  
>>>> (from which I recommend Neuron
>>>> 2007 56:226-238 for its broad scope) that we need to know how it  
>>>> is wired where 'it' may be
>>>> neocortex, thalamus, olfactory cortex or even bug whateveritis-ex.
>>>>
>>>> Framed computationally this could involve wiring exploration  
>>>> (which we are doing lately) or
>>>> development algorithms or new Hebb variants.  Of course, without  
>>>> the accompanying
>>>> physiological/anatomical exploration this will be meaningless.
>>>>
>>>> Admittedly this is a rather low-level question without the grand  
>>>> sweep of a Hilbert q. but
>>>> then biology is often grubby (even literally) rather than ethereal.
>>>>
>>>> Bill
>>>>
>>>> -- 
>>>> William W. Lytton, MD
>>>> Professor of Physiology, Pharmacology, Biomedical Engineering,  
>>>> Neurology
>>>> State University of NY, Downstate Medical Center, Brooklyn, NY
>>>> billl at neurosim.downstate.edu http://it.neurosim.downstate.edu/ 
>>>> ~billl
>>>> ________________________________________________________________
>>>
>>>
>>>
>>>
>>> ==================================
>>>
>>> Dr. James M. Bower Ph.D.
>>>
>>> Professor of Computational Neuroscience
>>>
>>> Research Imaging Center
>>> University of Texas Health Science Center -
>>> -  San Antonio
>>> 8403 Floyd Curl Drive
>>> San Antonio Texas  78284-6240
>>>
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>>
>
>
>
>
> ==================================
>
> Dr. James M. Bower Ph.D.
>
> Professor of Computational Neuroscience
>
> Research Imaging Center
> University of Texas Health Science Center -
> -  San Antonio
> 8403 Floyd Curl Drive
> San Antonio Texas  78284-6240
>
> Main Number:  210- 567-8100
> Fax: 210 567-8152
> Mobile:  210-382-0553
>
> CONFIDENTIAL NOTICE:
> The contents of this email and any attachments to it may be  
> privileged or
> contain privileged and confidential information. This information is  
> only
> for the viewing or use of the intended recipient. If you have  
> received this
> e-mail in error or are not the intended recipient, you are hereby  
> notified
> that any disclosure, copying, distribution or use of, or the taking  
> of any
> action in reliance upon, any of the information contained in this e- 
> mail, or
> any of the attachments to this e-mail, is strictly prohibited and  
> that this
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> immediately returned to the sender or destroyed and, in either case,  
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> e-mail and all attachments to this e-mail must be immediately  
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