In the past two decades, we have seen unprecedented advances in studying the human brain. Perhaps the most exciting has been the advent of structural and functional brain imaging techniques, which have revolutionized cognitive and behavioral neuroscience by allowing us a window into the brain activity underlying complex human behaviors. These technological advances have also led to the swift translation of basic neuroscience findings into more targeted therapies for clinical practice.
There is a wide variety of brain imaging techniques, which can be classified into three major categories: (1) nuclear medicine imaging techniques, including positron emission tomography (PET) and single photon emission computed tomography (SPECT); (2) magnetic resonance imaging (MRI) techniques including structural MRI, functional MRI (fMRI), and MR spectroscopy; and (3) electrophysiological imaging techniques, which include electroencephalography (EEG) and magnetoencephalography (MEG). Each of these techniques reveals a different aspect of brain structure and/or function, yielding a breadth of knowledge about the biochemical, electrophysiological, and functional processes of the brain; neurotransmitter activity; energy utilization and blood flow; and drug distribution and kinetics. Together they shed light on complex neuropsychological diseases, including drug addiction.
Addiction is a chronically relapsing disease characterized by drug intoxication, craving, bingeing, and withdrawal with loss of control over drug-related behaviors. This cycle culminates in the escalated preoccupation with the attainment and consumption of the substance. While the compulsion to consume the drug increases, the seeking of other (healthier) rewards (e.g., social experiences, exercise) in the environment decreases leading to detrimental consequences to the individual’s well-being (encompassing physical health and other personal, social, and occupational goals). The Impaired Response Inhibition and Salience Attribution (iRISA) model of drug addiction (Goldstein and Volkow, 2002
) posits that the cycle is characterized by impairments of two broad behavioral systems – response inhibition and salience attribution. According to the iRISA model, the salience and value attributed to the drug of choice and associated conditioned stimuli is much higher than the value attributed to other non-drug reinforcers, which in turn is associated with a decrease in self-control.
Drugs of abuse increase mesolimbic and mesocortical dopamine (DA) levels, which is crucial for their reinforcing effects (Koob et al., 1994
; Di Chiara, 1998
). Drugs of abuse exert their reinforcing and addictive effects by directly triggering supraphysiological DA action (Bassareo et al., 2002
) and indirectly, by modulating other neurotransmitters [e.g., glutamate, γ aminobutyric acid (GABA), opioids, acetylcholine, cannabinoids and serotonin] in the reward circuit of the brain (see Koob and Volkow, 2010
for a review). With chronic drug use, DA D 2
receptor availability is reduced (Volkow et al., 1990a
; Nader and Czoty, 2005
; Nader et al., 2006
), altering function in dopaminergically innervated corticolimbic areas [encompassing the orbitofrontal cortex (OFC) and anterior cingulate cortex (ACC)] that mediate processing of reward salience, motivation, and inhibitory control (Volkow et al., 1993a
; McClure et al., 2004
; Goldstein et al., 2007a
Here, we summarize PET, fMRI and EEG studies of the brain systems underlying human behaviors that are associated with the drug addiction syndrome. Hundreds of papers were potentially appropriate for this review and, of necessity, we had to be selective. To provide the reader with a general perspective of the rapid advances, we have chosen to highlight only key behavioral domains, including intoxication, drug craving, bingeing, withdrawal, abstinence, and relapse, with an illustrative blend of neuroimaging studies across several drugs of abuse.