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Functional Brain Imaging in Drug Studies

This course delves into using functional brain maps to study drug effects. Topics include dopamine, neuroleptic drugs, spatial resolution, and more.

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Functional Brain Imaging in Drug Studies

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  1. Imaging Drugs in the BrainENAS 880 / NSCI 523Fall 2010Morris/Cosgroveevan.morris@yale.edukelly cosgrove@yale.eduhttp://tauruspet.med.yale.edu/staff/edm42/courses/ENAS_880/index.htmlQuiz 1

  2. 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? Course business

  3. dopamine neuroleptic tomographic method spatial resolution cyclotron (‘in-hospital’… why) specific activity specific binding attentuation correction septa reference region Terms in first papers 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. now this functional image overlaid on a structural image: the ‘pixels’ in a structural image convey some physical, anatomical, or geographical information about the object. http://www.cscs.umich.edu/~crshalizi/election/

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

  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. 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.” Carboni et al, J Neurosci 20:RC102(1-5), 2000

  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. BP = B/F at steady state Schematic Diagram of Ligand Binding “Rest” condition endogenous NT unlabeled tracer radiolabeled tracer

  22. Schematic Diagram of Ligand Binding “Rest” condition loss of receptors BP ↓ endogenous NT unlabeled tracer radiolabeled tracer

  23. Schematic Diagram of Ligand Binding DA-release condition DA ↑ BP ↓ endogenous NT unlabeled tracer radiolabeled tracer

  24. DBP is the (fractional) difference in BP between conditions DBP= (BP1-BP2)/BP1

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

  26. questions (2)

  27. questions (3)

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