In article <CNmdnVIaJq9AJwbcRVn-hw at giganews.com>,
"MZ" <zarellam at removetwcny.rr.comspam> wrote:
> > There's no proven
> > causal chain between, say, a neuron firing more actively and a change in
> > the amount of oxygenated blood flowing through the nearest capillary.
>> Neurovascular coupling has been demonstrated quite thoroughly by Grinvald's
> group (among others), I believe. I have Villringer and Dirnagl (1995)
> written down. May be time to review it.
Yes, I forgot I was taking a shot at optical imaging as well! As I
mentioned, this is not my area of expertise. That article looks
interesting but isn't accessible at my institution, which is a shame.
Can you recommend any others?
When I say "causal chain", I mean a chain of cellular events which start
with increased numbers of action potentials, and specify how that causes
vasodilatation. Is that elucidated? What's the messenger that dilates
capillaries? What secretes it? Under what conditions is it secreted?
> > 2. As far as I know, the mechanism by which blood flow is altered is not
> > understood. It is likely to be strongly mediated by astrocytes, whose
> > processes wrap brain capillaries in continuous sheaths, and hence would
> > be controlled by glial cells, rather than neurons. Hence it seems
> > likely that the needs of glia are more relevant to fMRI than the
> > activity of neurons directly.
>> I think it's been shown that action potential propagation and synaptic
> transmission require the bulk of the ATP available and are therefore
> responsible for the hemodynamic signal.
Action potentials using up the bulk of ATP doesn't automatically mean
that they will cause a change in the blood flow, of course - it may
involve mobilisation of internal energy stores, etc. depending on the
type or duration of activity.
> This doesn't address blood flow
> specifically, though. However, recent evidence has demonstrated that the
> fMRI signal can also exhibit the earlier oxymetry signal, and that the two
> appear to be correlated.
The technique is measuring changes in oxyhaemoglobin density, so that's
not surprising. I don't mean to say there is strong evidence that blood
flow changes are NOT related to changes in neural activity, just that
too many non-physiological researchers accept it blindly as a marker of
general "activity". It's a marker of haemodynamic activity, all right,
but that doesn't rigorously imply increased neural activity (whatever
that means in the context of brain function anyway!). ECT induces huge
neural activity and increased blood flow, but those things sure aren't
functional.
> Regardless, the concern does become whether or not
> one can pull out inhibitory responses from the overall signal, if synaptic
> transmission is indeed a major component.
How could you ever do that? I don't think it's even an issue -
GABAergic neurons use the same fuel as any other, so it's not possible
to split them apart using gross measures of energy consumption. It'd be
like trying to tell male from female statistics when looking at a city's
electricity consumption.
> > but there's no way to
> > adjust for the real differences in regional function between
> > individuals, which have been demonstrated anatomically and
> > physiologically but don't show up on MRI.
>> The possible exception would be found in the rare cases when intraoperative
> techniques such as microstimulation/recording and optical imaging can be
> used to verify things that fMRI doesn't have the spatial resolution to
> attain.
Yes, I agree, and there are things I have read recently which attempt
this kind of thing. I reckon you would agree that it's not much help
trying to scale from extracellular recordings to the energy demands of
millions of neurons though.
> > 4. Nobody has any idea if blood flow is modulated by the *type* of
> > processing in a given region - aside from the ignorant people who
> > believe we only use 10% of our brains, most neuroscientists would agree
> > that even during "resting", there is sustained and large scale activity
> > in the nervous system, and we are looking for fluctuations on a much
> > smaller scale, which may or may not be relevant to what the region is
> > doing. For instance, active suppression of activity in a region is
> > almost certainly more metabolically expensive than normal processing, so
> > a strongly suppressed area would show up as more "active" on an fMRI
> > scan. Histological stains which show markers of high metabolic need are
> > usually labelling inhibitory neurons, which tells us who the major
> > "blood consumers" are in the brain.
If I may argue with myself here, a friend disputed this (which I had
thought was my best point) by saying "well, if it IS increased
inhibition, who's not to say that increased inhibition isn't the most
important type of activity in the brain"? I had to agree.
> > 5. Similarly, it is possible that changes in patterns of activity,
> > rather than the overall amount of activity, could be far more relevant
> > in processing tasks and stimuli. The idea of synchronisation has been
> > widely proposed as a way that processes could be "bound" together in
> > consciousness, but that only involves altering the timing of spikes, not
> > the overall number. Presumably that wouldn't show up on fMRI at all,
> > since the tissue's metabolic demands would be unchanged.
>> Even in most electrophysiological studies those ideas aren't examined.
> People play with rate coding more often than not (and perhaps more often
> than they should). fMRI, however, could provide some insights into
> spontaneous activity. Optical imaging has revealed highly structured maps
> (corresponding to orientation maps) in visual cortex in the absence of
> stimulation. Surely fMRI is also showing something - we just don't know
> what it is yet.
You're right about electrophys - we just count rates most of the time!
I read a paper showing that visual stimuli on a CRT monitor lead to
spike trains which are largely locked to the 60Hz refresh rate, and one
colleague's response was essentially "so what, if we get a difference in
spike counts?"
I agree of course that fMRI shows a real phenomenon worthy of
understanding, but I dislike the laziness which leads to people treating
it as a live picture of the brain thinking. I don't disagree at all
with a lot of what you have written, in fact it's precisely this kind of
exchange that I think more people should be having in regard to fMRI.
Writing the earlier post has led to me discussing the issues offline
with people whose knowledge I respect, and it's changing my
understanding ... as you are of course, too!
> <snip>
> I share your sentiment about the shortcomings of the technique though. As
> for the original comment/question about the brain surface, the columnar
> architecture of the cortex has lulled many folks into the idea that knowing
> what's going on in one layer is sufficient. Maybe that's true; with the
> kind of resolution we're talking about, a single voxel is often
> incorporating the entire depth of the cortex. But other methods that
> examine hemodynamic responses, like optical imaging, maybe it's not such a
> wise strategy?
Well, you've only got to look at the studies comparing activity in
different layers to see how right you are on that score.
Thanks for injecting some rigour into the discussion.
Cheers,
Matthew.
