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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EmptyBox Feeding

Di Chiara et al.

FOOD

VTA/SNnucleus accumbens

frontalcortex

Dopamine Neurotransmission

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180o

511 kev 511 kev

18FDG

Radiotracer PET Scanner PET Image

UCLA

Ovarian Cancer lung metastases

Positron Emission Tomography (PET)

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Reward Circuits

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Reward Circuits

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Non-Drug Abuser

Heroin

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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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CG

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P < 0.005

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Volkow et al., AJP, 1999.

Brain Glucose Metabolism in Cocaine Abusers (n=20) and Controls (n=23)

Striatum

CG

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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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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

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AttentionWorkingmemory

Visual tracking

fMRI signals

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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

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GODrive

Memory

Saliency

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Saliency

Adapted from: Volkow et al., J Clin Invest 2003.

Addicted Brain