Imaging Drugs in the BrainENAS 880 / NSCI 523

Fall 2010Morris/Cosgrove

evan.morris@yale.edukelly cosgrove@yale.edu

http://tauruspet.med.yale.edu/staff/edm42/courses/ENAS_880/index.html

Quiz 1

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?

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

Warmup: What is this?

http://www.cscs.umich.edu/~crshalizi/

OK, start with this…

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

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

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/

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

action

what’s going on here?

Christian et al.

which ones are…functional vs structural

which ones do “detection” vs “characterization”

Fowler et al., Science & Practice Perspectives, April 2007, 4-16

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

what’s the prominent neurotransmitter in the nucleus accumbens?

Fowler et al., Science & Practice Perspectives, April 2007, 4-16

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.”

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

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

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

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

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

Schematic Diagram of Ligand Binding

“Rest” condition

endogenous NT unlabeled tracer radiolabeled tracer

BP = B/F at steady state

Schematic Diagram of Ligand Binding

“Rest” condition

endogenous NT unlabeled tracer radiolabeled tracer

loss of receptors

BP ↓

Schematic Diagram of Ligand Binding

DA-release condition

endogenous NT unlabeled tracer radiolabeled tracer

DA ↑

BP ↓

BP is the (fractional) difference in BP between conditions

BP= (BP1-BP2)/BP1