What are some of the issues in choosing bolus vs bolus+infusion? Which one predicts equilibrium coefficients? Which one achieves equilibrium? Which one is more difficult, experimentally? Which is more difficult to analyze – mathematically? Which would be good for a slow tracer? Which would be good for a fast tracer? Which one is cheaper? Which one is good for a studying the effect of horse-riding on striatal dopamine? Which one …. for studying distribution of receptors in equestrians? Which one …. for an irreversible tracer?

what was the general argument here? what were the assumptions?

model similar to prev. like Morris paper, they allow for time-varying dopamine but here, the function is preset and the assumption is that DA is always in equilib between free and bound. DA(t) is an exponential that peaks instantaneously at start of stimulus. Is this realistic?

involved model of noise in  BP does it make sense? Noise goes down with more counts (NEC) in either the Reference region or the target region. Noise goes down with pixel size of the regions Noise goes down as the ratio of the target to reference region goes up.

want to optimize the sampling of the pre-stimulus equilib value and the post-stimulus equilib value given lots of simulations based on differing input functions, we can ask, what are the best overall windows for pre and post Trade-offs longer values means more counts, better statistics – but perhaps more bias too. later windows mean closer to equilib – less bias but worse statistics Why doesn’t the post-stim curve stay flat? Does it ever?

major finding of Watabe 2000: optimal sampling of B/I data pre and post stim gives better significance, larger effect size, fewer subjects required. where is most of the gain – why?

H is the transfer function for a B/I study. Ie., the tissue response to an arbitrary input. It is made up of the response to a bolus (  ) (aka the impulse response) and the response to an infusion (step) (aka the step response) response to : = response to : = Kbol tells us how much bolus response and how much infusion response we want – usually to get to equilib in tissue fastest… but not all tissues behave the same way, so it’s a compromise. Kbol is in units of minutes because a bolus is characterized by a dose but an infusion is characterized by a dose/time

Estimated K bol from bolus tissue responses --- same (female) subject

Issues: B vs B/I anesthesia dependence self-admin SA is it high or low? hint:

Early or Late (monkey 11 C-raclopride images)

BP image

? ? Fill in the boxes to explain the paradigms

? ? plot the curves to show the dynamic 11 C-raclopride data in dorsal anterior caudate

why correct for vascular contrib? why didn’t they do it in bolus case?

where is the activation? does this make sense? why do they call this exploratory? what are the general steps to get to this point? what correction has to be made? why do we need to normalize all the data ‘spatially’ first? what is a t value?