Addiction as a brain disease Brain Imaging in Addictions
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Transcript of Addiction as a brain disease Brain Imaging in Addictions
Addiction as a brain disease
Brain Imaging in AddictionsGene-Jack Wang, MD
Professor of Radiology, Stony Brook University
Sr. Scientist, Bioscience Department, Brookhaven National Laboratory
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0 1 2 3 4 5 hrTime After Amphetamine
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f B
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se
AMPHETAMINE
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% o
f B
asal
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ease
EmptyBox Feeding
Di Chiara et al.
FOOD
VTA/SNnucleus accumbens
frontalcortex
Dopamine Neurotransmission
+ -
180o
511 kev 511 kev
18FDG
Radiotracer PET Scanner PET Image
UCLA
Ovarian Cancer lung metastases
Positron Emission Tomography (PET)
Cocaine
Alcohol
DA
DA
DA
DA DA DA
DA
Reward Circuits
DA DA DA DA
DA
Reward Circuits
DA
DA
DA
DA DA
DA
Drug Abuser
Non-Drug Abuser
Heroin
Meth
Volkow et al., 2002.
Dopamine D2 Receptors are Lower in Addiction
Decreased dopamine activity predicts relapse in methamphetamine abusers
• METH abusers with better DA function during the early withdrawal period were more likely to stay sober at follow up than those with low striatal DA function.
• This finding suggests that poor DA function may be a biomarker that predicts a greater likelihood for relapse and a greater addiction severity.
• Thus early detection of the extent of DA dysfunction may be helpful in predicting clinical outcomes.
Wang et al, Mol Psychiatry, 2011
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Controls Abusers
mic
rom
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min
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Controls Abusers
mic
rom
ol/1
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min
CG
OFC
CG
P < 0.005
P < 0.01
Volkow et al., AJP, 1999.
Brain Glucose Metabolism in Cocaine Abusers (n=20) and Controls (n=23)
Striatum
CG
PreF
OFC 3035404550556065
1.8 2 2.2 2.4 2.6 2.8 3 3.2 3.4DA D2 Receptors (Ratio Index)
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ol/1
00g/
min
r = 0.7, p < 0.001
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2.9 3 3.1 3.2 3.3 3.4 3.5 3.6
OF
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umol
/100
gr/m
in
DA D2 Receptors (Bmax/kd)
Cocaine Abusers
r = 0.7, p < 0.005
METH Abusers
control Volkow et al., AJP 2001.
Correlations Between D2 Receptors in Striatum and Brain Glucose Metabolism
cocaine abuser
Non-ionizing Radiation; > 104 units worldwide; >108 MRI scans/year
Magnetic Resonance Imaging (MRI)
Brain activation and deactivation patternsBrain activation and deactivation patterns
0 20 40 60 80 100 120-2
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AttentionWorkingmemory
Visual tracking
fMRI signals
time
Coordinate based meta-analyses of fMRI studies
Tomasi et al, Crit Rev Biochem Mol Biol. 2013
From 44 published studies
From 13 published studies
Published studies between 2001 and 2011
Tomasi et al, Neuroimage, 2011
Functional connectivity hubs in the human brain
• Cocaine abusers have lower resting state functional connectivity (rsFC) of midbrain with thalamus, cerebellum and anterior cingulate than controls.
• This is associated with decreased activation in thalamus and cerebellum and enhanced deactivation in rostral cingulate.
Tomasi et al, PLOS One, 2010
Years of cocaine use lower tsFC of midbrain with thalamus
20 cocaine abusers and 20 controls
Disrupted Functional Connectivity with Dopaminergic Midbrain in Cocaine Abusers
DriveOFC
Saliency NAc
MemoryAmygdala
Control CG
Non-Addicted Brain
STOP
GODrive
Memory
Saliency
Control
Drive
Memory
Saliency
Adapted from: Volkow et al., J Clin Invest 2003.
Addicted Brain