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Subject:

Re: advantages of PET over fMRI for drug studies? (fwd)

From:

Andrew Lawrence <[log in to unmask]>

Reply-To:

Andrew Lawrence <[log in to unmask]>

Date:

Wed, 22 Mar 2000 17:11:26 +0000

Content-Type:

text/plain

Parts/Attachments:

Parts/Attachments

text/plain (91 lines)

At 12:27 PM 3/22/00 -0600, you wrote:
>Dear Eric
>
>>> vascalature.  If there are differential effects of the drug (relative to
>>> placebo) on your two (or more) different cognitive states it's
difficult to
>>> continue arguing for a non-specific vascular effect.
>>
>>
>>I think it is important to keep in mind the possibility of a
>>pharmacologic effect on the gain of the vascular response to neural activity
>>changes. Such a mechanism would be manifest as an interaction of 
>>task and pharmacologic treatment.
>
>Perhaps I didn't explain what I meant clearly enough, and anyway please
>correct me if I'm wrong, but isn't your argument true only if the drug
>affects the *entire* network that is normally activated by the task?  
>
>For example, if a Task-Control comparison activated regions A, B & C under
>placebo conditions, and then the drug affects area A only, does your
>argument still apply?
>
>As far as I can see, a REGIONALLY-specific task x drug interaction cannot
>be explained by a non-specific (ie. not regionally specific) effect of drug
>on the neurovascular pattern.  In other words, to demonstrate a drug x task
>interaction (from which one can make cognitive inferences) the areas
>activated/deactivated by the interaction term should not be identical to
>those produced by the main effect of the task.
>
>Best wishes
>
>
>Jenny
>
> 
>
>
>
>
>-----------------------------------------------------------
>
>Dr. Jennifer T Coull
>Senior Research Fellow
>
>Wellcome Department of Cognitive Neurology
>Institute of Neurology
>12 Queen Square
>London WC1N 3BG
>UK
>
>phone: +44 171 833 7484
>fax:   +44 171 813 1420
>
>
Dear Jenny,

Following on from Eric's point and your comment, I think that it is
entirely possible that the gain function in different regions might be
different, rather than homogenous across the entire brain (although I'm
certainly no expert on the brain vasculature!), and so one could still see
regionally specific effects due to drug actions on vascular, rather than
neural responses. The fundamental point is that the relationship between
neural activity, neuromodulation, and hemodynamics is unclear. 

A different methodology, which several groups are working on, is to examine
changes in the binding / kinetics of radioligands (such as the D2 ligand
raclopride) in relation to cognitive challenge. Of course, this technique
has its own problems of interpretation (such as the potentially confounding
effects of changes in blood flow, etc, and the need to integrate activity
over a long time range). 

Clearly, none of these techniques is optimal, and more work will be needed
on modeling the relationship between neuromodulation, neural activity, and
PET/ fMRI signal change before any definitive statements can be made.

Best wishes,


Andrew

_____________________________________________
Andrew Lawrence PhD,
MRC Cognition and Brain Sciences Unit,
15 Chaucer Rd,
Cambridge CB2 2EF,
UK



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