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Imaging Drugs in the BrainENAS 880 / NSCI 523
Fall 2010Morris/Cosgrove
[email protected] [email protected]
http://tauruspet.med.yale.edu/staff/edm42/courses/ENAS_880/index.html
Quiz 1
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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?
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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
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Warmup: What is this?
http://www.cscs.umich.edu/~crshalizi/
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OK, start with this…
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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
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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
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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/
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Our goal: Understand how functional maps of the human brain are used to study drugs and drug
action
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what’s going on here?
Christian et al.
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which ones are…functional vs structural
which ones do “detection” vs “characterization”
Fowler et al., Science & Practice Perspectives, April 2007, 4-16
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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
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what’s the prominent neurotransmitter in the nucleus accumbens?
Fowler et al., Science & Practice Perspectives, April 2007, 4-16
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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.”
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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
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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?
Fowler et al., Science & Practice Perspectives, April 2007, 4-16
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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
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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
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why is most of the brain blue?
are these images from the start or the
end of the experiment?
is this structural or functional?
is this a ‘detection’ or a
‘characterization’ experiment?
Fowler et al., Science & Practice Perspectives, April 2007, 4-16
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Schematic Diagram of Ligand Binding
“Rest” condition
endogenous NT unlabeled tracer radiolabeled tracer
BP = B/F at steady state
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Schematic Diagram of Ligand Binding
“Rest” condition
endogenous NT unlabeled tracer radiolabeled tracer
loss of receptors
BP ↓
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Schematic Diagram of Ligand Binding
DA-release condition
endogenous NT unlabeled tracer radiolabeled tracer
DA ↑
BP ↓
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BP is the (fractional) difference in BP between conditions
BP= (BP1-BP2)/BP1