1. Imaging Drugs in the Brain ENAS 880 / NSCI 523 Fall 2010 Morris/Cosgrove evan.morris@yale.edu kelly cosgrove@yale.edu http://tauruspet.med.yale.edu/staff/edm42/courses/ENAS_880/index.html Quiz 1 evan.morris@yale.edu http://tauruspet.med.yale.edu/staff/edm42/courses/ENAS_880/index.html

2. Course business info posted on Evan’s website a few classes in N203 at end of semester lectur-ettes, followed by… paper discussions – participation expected paper synopses to be written, emailed collaborative presentation or other work what are your interests? what are your goals?

3. Terms in first papers dopamine neuroleptic tomographic method spatial resolution cyclotron (‘in-hospital’… why) specific activity specific binding attentuation correction septa reference region recovery coefficient ligand vs tracer vs isotope contrast noise model compartments steady state structural vs functional caudate, cerebellum

4. Warmup: What is this? http://www.cscs.umich.edu/~crshalizi/

5. OK, start with this…

6. http://www.cscs.umich.edu/~crshalizi/election/ functional image overlaid on a structural image : the ‘pixels’ in a structural image convey some physical, anatomical, or geographical information about the object. now this

7. http://www.cscs.umich.edu/~crshalizi/election/ functional image : the color and size of the ‘pixels’ convey some functional information about how the object WORKS. now this

8. Electoral Map (Cartogram) Every county is displayed in color according to vote (in 2004) of the majority of the voters. The size of the county represents the number of voters. (Note that the western plain states are smaller than the east coast.) In this case, the cartogram shows us that –contrary to popular belief- the country’s distribution of Dems and Repubs was reasonably heterogeneous. http://www.cscs.umich.edu/~crshalizi/

9. but do “functional images” of the brain ever change the apparent shape of the brain?..actually, yes… perhaps we’ll get to this advanced topic this semester

10. Our goal: Understand how functional maps of the human brain are used to study drugs and drug action

11. what’s going on here? Christian et al.

12. which ones are…functional vs structural which ones do “detection” vs “characterization” Fowler et al., Science & Practice Perspectives, April 2007, 4-16

13. what’s the modality? what is the orientation of the brain? what is the orientation of the person? what’s the yellow stuff? is this a single subject? Fowler et al., Science & Practice Perspectives, April 2007, 4-16

14. what’s the prominent neurotransmitter in the nucleus accumbens? Fowler et al., Science & Practice Perspectives, April 2007, 4-16

15. Carboni et al, J Neurosci 20:RC102(1-5), 2000 Many drugs cause release of dopamine “… cocaine, morphine, nicotine, and ethanol share the property of increasing DA transmission in the BNST. This effect may be related to an action at the level of neuronal circuits activated by natural reinforcers … suggest[ing] that DA transmission of the BNST plays a role in the mechanism of drug abuse and addiction.”

16. is everyone familiar with this diagram? to what other site(s) could we direct a tracer? Fowler et al., Science & Practice Perspectives, April 2007, 4-16

17. which one is specific for neurotransmitter system? which one is a non-specific marker of ‘activation’? what are they ‘tracing’ are these molecules biologically the same as their tracees? is there a mistake on this slide? Fowler et al., Science & Practice Perspectives, April 2007, 4-16

18. which end is up? which end has high uptake in healthy controls? how do you know? what does that mean? why are these images so blurry? Fowler et al., Science & Practice Perspectives, April 2007, 4-16

19. what is the claim here? what assumption(s) is(are) at work? are they measuring the phenomenon or something related to it? Fowler et al., Science & Practice Perspectives, April 2007, 4-16

20. why is most of the brain blue? are these “early” or “late” images? is this structural or functional? is this a ‘detection’ or a ‘characterization’ experiment? Fowler et al., Science & Practice Perspectives, April 2007, 4-16

21. Schematic Diagram of Ligand Binding “Rest” condition endogenous NTunlabeled tracerradiolabeled tracer BP = B/F at steady state

22. Schematic Diagram of Ligand Binding “Rest” condition endogenous NTunlabeled tracerradiolabeled tracer loss of receptors BP ↓

23. Schematic Diagram of Ligand Binding DA-release condition endogenous NTunlabeled tracerradiolabeled tracer DA ↑ BP ↓

24.  BP is the (fractional) difference in BP between conditions  BP= (BP 1 -BP 2 )/BP 1

25. questions/thoughts on the review article by Fowler et al.

26. questions (2)

27. questions (3)